| 1. |
- Ackermann, Paul, et al.
(författare)
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An opioid system in connective tissue : A study of Achilles tendon in the rat
- 2001
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Ingår i: Journal of Histochemistry and Cytochemistry. - : SAGE Publications. - 0022-1554 .- 1551-5044. ; 49:11, s. 1387-1395
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of endogenous opioids and their receptors in rat achilles tendon was analyzed by immunohistochemistry (IHC), radioimmunoassay (RIA), and in vitro binding assays. The investigation focused on four enkephalins, dynorphin B, and nociceptin/orphanin FQ. Nerve fibers immunoreactive to all enkephalins (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Gly-Lys, Met-enkephalin-Arg-Phe) were consistently found in the loose connective tissue and the paratenon, whereas dynorphin B and nociceptin/orphanin FQ could not be detected. The majority of enkephalin-positive nerve fibers exhibited varicosities predominantly seen in blood vessel walls. Measurable levels of Met-enkephalin-Arg-Phe and nociceptin/orphanin FQ were found in tendon tissue using RIA, whereas dynorphin B could not be detected. In addition to the endogenous opioids identified, delta -opioid receptors on nerve fibers were also detected by IHC. Binding assays to characterize the opioid binding sites showed that they were specific and saturable for [H-3]-naloxone (K-d 7.01 +/- 0.98 nM; B-max 23.52 +/- 2.23 fmol/mg protein). Our study demonstrates the occurrence of an opioid system in rat achilles tendon, which may be assumed to be present also in other connective tissues of the locomotor apparatus. This system may prove to be a useful target for pharmacological therapy in painful and inflammatory conditions by new drugs acting selectively in the periphery.
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| 2. |
- Bergström, Jonas, et al.
(författare)
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Purification and quantification of opioid peptides in bone and joint tissues : a methodological study in the rat
- 2003
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 21:3, s. 465-469
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of methionine-enkephalin-Arg(6)-Phe(7) (MEAP) and dynorphin B (DYNB) representing two main precursors of opioids was analyzed in specimens from rat cortical bone, periosteum, bone marrow and joint tissue by radioimmunoassay (RIA). MEAP and DYNB were extracted in a solution of 4% EDTA in 2 M acetic acid previously proven suitable for extraction of sensory and autonomic neuropeptides in bone and joints. In crude extracts of cortical bone, the immunoreactive (ir) levels of both opioids were under the detection limit of RIA. As for DYNB this also applied to crude extracts of joints and periosteum. Therefore, two purification methods were tested and compared, i.e. reverse phase C 18 and ion exchange chromatography. RIA of the elution fraction disclosed a significant difference between the two methods in terms of recovery, i.e. <5% and 50%, respectively. Thus, purification by ion exchange chromatography prior to RIA appeared to be the most suitable by providing measurable levels of both MEAP and DYNB in all tissues analyzed (highest in bone marrow, lowest in cortical bone). The described method offers a means of quantifying opioid peptides in bone and joints, which may be utilized in the analysis of regulatory mechanisms of nociception, growth and immune responses in different conditions.
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| 3. |
- Broberger, Christian, et al.
(författare)
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Differential effects of intrastriatally infused fully and endcap phosphorothioate antisense oligonucleotides on morphology, histochemistry and prodynorphin expression in rat brain
- 2000
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Ingår i: Brain Research. Molecular Brain Research. - : Elsevier BV. - 0169-328X .- 1872-6941. ; 75:1, s. 25-45
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigated the selectivity and specificity associated with continuous intrastriatal treatment with antisense oligonucleotides. Rats were given intrastriatal infusions for 72 h with phosphodiester, and fully and endcap phosphorothioated oligonucleotide probes complementary to prodynorphin mRNA. Dynorphin (Dyn) peptide levels were measured by radioimmunoassay. The integrity of three other striatal transmitter systems, the neuropeptide Y (NPY)-ergic interneurons, the cholinergic interneurons and the dopaminergic afferent innervation, was assessed histochemically. The gross morphology of the striatum and the distribution of fluorescently labelled antisense probes were also investigated. Brains infused with phosphodiester probes had tissue Dyn levels not different from control. They also showed little or no change in staining for NPY, acetylcholinesterase (AChE) and tyrosine hydroxylase (TH) and essentially normal striatal gross morphology. In contrast, brains treated with fully phosphorothioated oligonucleotides showed significant decreases in striatal Dyn levels but also severe tissue damage accompanied by massive cell infiltration and decreases in immunoreactivities for the striatal neurochemical markers. Fluorescently labelled phosphorothioate probes were observed widely in the striatum and adjacent structures and, presumably retrogradely transported, in the dopamine cell bodies in the substantia nigra, also revealing the presence of abnormal cellular structures within the striatum. By comparison, endcap probes significantly reduced striatal Dyn levels and showed good tissue penetration without inducing major changes in tissue morphology or histochemistry of non-dynorphinergic systems, except for cell infiltration. The deleterious tissue effects of fully phosphorothioated oligonucleotides and the ineffectiveness of phosphodiester oligonucleotides in inhibiting protein synthesis suggest that, of the probes examined in this study, endcap oligonucleotides are the most useful for in vivo studies in the central nervous system.
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| 4. |
- Bytner, Beta, et al.
(författare)
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Nociceptin/orphanin FQ into the rat periaqueductal gray decreases the withdrawal latency to heat and loading, an effect reversed by (Nphe1)nociceptin(1-13)NH2
- 2001
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 922:1, s. 118-124
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the effect of intraperiaqueductal grey injection of nociceptin/orphanin FQ (N/OFQ) and an antagonist (Nphe(1))nociceptin(1-13)NH(2) on the hindpaw withdrawal response to thermal and mechanical stimulation in rats. N/OFQ (5 nmol) significantly decreased the nociceptive thresholds in both tests and 1, 5 and 10 nmol of (Nphe(1))nociceptin(1-13)NH(2) significantly reversed this effect in a dose dependent way. Our results demonstrate, that N/OFQ has a nociceptive action, possibly through inhibition of PAG neurons. This effect is blocked by the antagonist (Nphe(1))nociceptin(1-13)NH(2) probably via ORL1 receptors in the periaqueductal grey.
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| 5. |
- Lindholm, Sara, et al.
(författare)
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Nociceptin/orphanin FQ tissue concentration in the rat brain : Effects of repeated ethanol administration at various post-treatment intervals
- 2002
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - 0278-5846 .- 1878-4216. ; 26:2, s. 303-306
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study short- and long-term effects of repeated ethanol administration on nociceptin/orphanin FQ (N/OFQ) tissue concentrations in rat brain with radioimmunoassay. Animals were given either ethanol (intraperitoneal) or saline for 13 consecutive days. N/OFQ levels were examined at 30 min, 5 days and 21 days after the last dose on day 13. Ethanol-treated rats had significantly decreased N/OFQ tissue concentration in the hippocampus at 30 min after the last dose. N/OFQ levels were decreased in the cingulate cortex at 5 days after cessation of ethanol administration whereas no significant changes were found at 21 days. There were no significant changes in N/OFQ tissue concentrations at any time point studied in the mesolimbic dopamine (DA) system, a brain area associated with ethanol-induced activation. However, the results indicate that repeated ethanol administration may induce short- and long-term changes in N/OFQ tissue concentrations in other brain regions innervated with dopaminergic neurons.
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| 6. |
- Lindholm, Sara, et al.
(författare)
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Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain
- 2000
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Ingår i: Alcohol. - 0741-8329 .- 1873-6823. ; 22:3, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we have shown that rats repeatedly treated with ethanol and/or cocaine have decreased kappa-opioid receptor mRNA levels in the mesolimbic system. The aim of the present study was to investigate the short- and long-term effects of repeated ethanol administration on opioid peptide concentrations in brain tissue of male Sprague-Dawley rats. Dynorphin B (1-13) (Dyn B) and Met-enkephalinArg(6)Phe(7) (MEAP), endogenous ligands to kappa- and delta-opioid receptors, respectively, were measured using radioimmunoassays. The rats were given either ethanol [intraperitoneal (ip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty minutes after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly decreased in the cingulate cortex. The MEAP tissue concentration was decreased in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentrations were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue concentrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days after the last ethanol dose. The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward.
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| 7. |
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| 8. |
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| 9. |
- Ploj, Karolina, et al.
(författare)
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Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice
- 2000
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Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 53:2, s. 219-226
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate the involvement of the opioid and nociceptin/orphanin FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid peptides dynorphin B (DYNB) and Met-enkephalin-Arg(6) Phe(7) (MEAP) were examined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were compared in the brain and the pituitary gland with basal levels in the alcohol-avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-administration on peptides were studied in the C57BL/6J mice. Compared to the DBA/2J mice, C57BL/6J mice had low immunoreactive (ir) levels of DYNB and MEAP in the nucleus accumbens, the hippocampus, and the substantia nigra, low ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cortex. Higher ir-DYNB levels in the pituitary gland and in the periaqueductal gray (PAG) and higher ir-N/OFQ levels in the frontal cortex and in the hippocampus were detected in C57BL/6J mice compared to the DBA/2J mice. After 4 weeks of voluntary alcohol consumption, only minor changes in steady-state peptide levels were identified. However, 5 days after the alcohol-drinking period, lower levels of all peptides were detected in the ventral tegmental area and ir-DYNB levels were also lower in the amygdala and in the substantia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the PAG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the amygdala and substantia nigra as compared to control C57BL/6J mice. This study demonstrates strain differences between C57BL/6J mice and DBA/2J mice that could contribute to divergent drug-taking behaviour, and it also demonstrates time- and structure-specific changes in neuropeptide levels after alcohol self-administration in the C57BL/6J mice.
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| 10. |
- Ploj, Karolina, et al.
(författare)
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Effects of maternal separation on brain nociceptin/orphanin FQ peptide levels in male Wistar rats
- 2002
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Ingår i: Pharmacology, Biochemistry and Behavior. - 0091-3057 .- 1873-5177. ; 73:1, s. 123-129
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Tidskriftsartikel (refereegranskat)abstract
- Environmental manipulation early in life may induce persistent alterations in adult behaviour and physiology. In this study, we investigated the long-term effects of daily maternal separation, Days 1-21, on brain immunoreactive nociceptin/orphanin FQ (ir-N/OFQ) levels in male Wistar rats. The rat pups were separated in litters for 360 min (MS360) or 15 min (H15). Control rats were left undisturbed until weaning. Peptide levels were measured at 10 weeks of age. In the hypothalamus and periaqueductal gray, MS360 induced an increase in ir-N/OFQ levels in comparison with control rats. H15 rats had increased ir-N/OFQ levels in the hypothalamus and the medial prefrontal cortex compared with control animals. The rats were also tested at two occasions in an elevated plus-maze. An increased anxiety-like behaviour was shown in MS360 rats at weaning, whereas a decreased anxiety response was found at 9 weeks of age compared with control rats. The study shows that early life experiences induce long-term effects on behaviour, as well as brain N/OFQ levels.
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| 11. |
- Ploj, Karolina, et al.
(författare)
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Effects of melanocortin receptor ligands on ethanol intake and opioid peptide levels in alcohol-preferring AA rats
- 2002
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Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 59:2, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- Melanocortin (MC) peptides are suggested to play a role in opiate dependence, where they antagonise the addictive properties of opiates. To further study the involvement of the MCs in drug dependence, we analysed the effects of the MC(4)-receptor antagonist HS014 (1 nmol/rat), and the non-selective MC-receptor agonist MTII (1 nmol/rat), using i.c.v. administration, on ethanol intake in alcohol-preferring AA rats. The rats had access to ethanol during 40 days, resulting in a mean ethanol intake of 6.6 g/kg/day, before treatment. One group received only artificial cerebrospinal fluid solution. MTII caused a reduction in ethanol intake and ethanol preference, whereas HS014 was without effect. No effect on water intake was observed. A decrease in food intake was detected after MTII, whereas HS014 induced an increase in food intake. Analysis of dynorphin B and Met-enkephalin-Arg(6)Phe(7) immunoreactive levels revealed that MTII and HS014 altered opioid peptide levels in several brain areas and the pituitary gland of the rats with an established ethanol intake. This is the first report showing that manipulation of the MC-receptor system changes ethanol intake in chronically ethanol-drinking AA rats. In addition, manipulation of the MC system modulates ethanol-induced changes in opioid peptide levels.
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| 12. |
- Ploj, Karolina, et al.
(författare)
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Effects of neonatal handling on nociceptin/orphanin FQ and opioid peptide levels in female rats
- 2001
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Ingår i: Pharmacology, Biochemistry and Behavior. - 0091-3057 .- 1873-5177. ; 69:1-2, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- Animals exposed to short periods of handling during the critical period of development, i.e., the first 21 days of life in rats, show attenuated neuroendocrine responses to stress in adult life. We have previously reported long-term changes in brain dynorphin (DYN) peptide levels in male Sprague-Dawley rats after neonatal handling. The purpose of this study was to investigate whether neonatal handling, 15-min individual separation from the mother during postnatal days 1-21, can induce long-term changes in DYNB, Met-enkephalin Arg(6)Phe(7) (MEAP) and nociceptin/orphanin FQ (N/OFQ) immunoreactive (ir) levels in female Sprague-Dawley rats. The peptides were measured in brain and pituitary gland 2 months after the handling procedure. The results reveal that handled (H) rats had increased ir levels of N/OFQ, DYNB and MEAP in the periaqueductal gray (PAG) as compared to nonhandled (NH) controls. Furthermore, H rats had decreased ir levels of DYNB in the frontal cortex and in the amygdala. In contrast to previous findings in male rats, DYNB levels were unaffected in areas related to the hypothalamo - pituitary - adrenal (HPA)-axis. The results indicate that a manipulation early in life can induce persistent neurochemical changes in the N/OFQ and opioid peptide system in female Sprague-Dawley rats.
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| 13. |
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| 14. |
- Ploj, Karolina, et al.
(författare)
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Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats
- 2003
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Ingår i: Neuropeptides. - 0143-4179 .- 1532-2785. ; 37:3, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- Environmental manipulations early in life may induce persistent alterations in adult behaviour and physiology. The underlying neural mechanisms of these responses are not yet clear. We have previously reported long-term changes in brain opioid peptide levels in male and female Sprague-Dawley rats after short periods (15 min, known as neonatal handling) of maternal separation (MS) until weaning. To study this further, we investigated behavioural and neurochemical effects of repeated MS in male Wistar rats. The rat pups were separated from their dams in litters for either 360 min (MS360) or 15 min (MS15) daily from postnatal day 1 to 21 or exposed to normal animal facility rearing. Behavioural analysis showed that MS360 rats had increased ultrasonic calls on postnatal day 5 compared to MS15 rats, but not on postnatal day 6. Moreover, the MS360 rats had more animals with higher frequency of calls at day 5 than 6 than the MS15 rats. Analysis of the opioid peptides dynorphin B and Met-enkephalin-Arg(6)Phe(7) with radioimmunoassay 7 weeks after the MS procedure, revealed long-term neurochemical changes in several brain areas and in the pituitary gland. Immunoreactive dynorphin B and Met-enkephalin-Arg(6)Phe(7) levels were affected in the hypothalamus and dynorphin B levels in the neurointermediate pituitary lobe, amygdala, substantia nigra and the periaqueductal gray. Together, these findings show that repeated periods of MS early in life in male Wistar rats affect the development of the ultrasonic call response and induce long-lasting and possibly permanent alterations in the opioid peptide systems.
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| 15. |
- Ploj, Karolina, et al.
(författare)
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Long-term effects on brain opioid and opioid receptor like-1 receptors after short periods of maternal separation in rats
- 2003
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Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 345:3, s. 195-197
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Tidskriftsartikel (refereegranskat)abstract
- Short periods of maternal separation of neonatal rats are known to induce attenuated behavioural and neuroendocrine responses to stress in adult life. The present study was carried out to evaluate whether 15 min separation from the dam during postnatal days 1-21 (MS15) can induce long-term changes in brain opioid (kappa- and delta-receptors) and opioid receptor-like 1 (ORL1) densities in male Sprague-Dawley rats. Receptor autoradiography indicated that MS15 rats had increased delta-receptor density in the basomedial amygdala compared to animal facility reared rats 2 months after MS15. No differences in brain kappa- or ORL1-receptor density were found. The results indicate that a manipulation early in life can induce persistent neurochemical changes in the delta-opioid receptor system, which suggests involvement of delta-opioid receptors in the altered emotional processing in these rats.
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| 16. |
- Roman, Erika, et al.
(författare)
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Maternal separation alters acquisition of ethanol intake in male ethanol-preferring AA rats
- 2003
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Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 27:1, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged daily maternal separation can increase the risk for developing substance abuse, whereas brief maternal separation has been reported to induce positive behavioral effects, decrease voluntary ethanol intake and induce long-lasting changes in brain opioid peptides. The ethanol-preferring AA (Alko, Alcohol) rats have altered basal levels of endogenous opioid peptides that may relate to their high voluntary ethanol intake. The purpose of this study was to investigate whether maternal separation could affect acquisition of ethanol intake in AA rats. METHODS: The rat pups were exposed to 15 min (MS15) or 360 min (MS360) of maternal separation during postnatal day 1-21, while control rats were exposed to normal animal facility rearing. As adults, the male rats were gradually introduced to increasing concentrations of ethanol. Furthermore, the effect of restraint stress on voluntary ethanol intake was investigated. RESULTS: The MS15 rats reached a high voluntary ethanol intake later than MS360 and control rats. The MS15 rats had a lower ethanol intake and preference at 8% ethanol compared to MS360 rats and lower ethanol intake compared to control rats. MS15 rats also had a lower 10% ethanol intake in comparison with MS360 rats. Restraint stress decreased the ethanol intake in MS15 and MS360 rats, whereas the ethanol intake in control rats was unaffected. CONCLUSIONS: We have previously shown that prolonged periods of maternal separation in Wistar rats result in an increased ethanol intake later in life. This was not repeated in this study, using AA rats with an inherent high ethanol intake. However, it is shown that brief maternal separation can delay acquisition of high ethanol intake and in addition decrease voluntary ethanol intake and preference in AA rats. Maternal separation for 15 min is therefore suggested to protect against high voluntary ethanol intake later in life.
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| 17. |
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| 18. |
- Roman, Erika, 1974-
(författare)
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Maternal Separation in Rats : An Experimental Model for Long-Term Effects of Early Life Experiences on Neurochemistry, Voluntary Ethanol Intake and Exploration and Risk Assessment Behavior
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The period of early life is important for the development of individual brain function and behavior. Human studies have shown altered vulnerability to develop psychopathology and/or excessive drug intake, possibly leading to dependence, as a consequence of early life experiences. In the present thesis, maternal separation (MS), an experimental model for studies of early environmental influences, was used to investigate long-term effects on neurochemistry, voluntary ethanol intake and exploration and risk assessment behavior in rats. Rat pups were assigned to one of three different rearing conditions: daily 15 min (MS15) or 360 min (MS360) of MS and normal animal facility rearing (AFR) during the first three weeks of life. Measurements of adult endogenous opioid peptide levels, opioid- and dopamine receptor density revealed minor MS-induced effects on the opioid system whereas interesting alterations were found in dopamine receptor density. Long-term effects on voluntary ethanol intake showed distinct MS-induced alterations in male Wistar and ethanol-preferring AA (Alko, Alcohol) rats. Female Wistar rats were unaffected, indicating sex differences in the effects of MS on ethanol intake. Male MS15 rats generally had a slower acquisition phase and a low subsequent ethanol intake whereas male MS360 rats had a high ethanol intake. MS15 is therefore suggested to protect against a high voluntary ethanol intake in male rats whereas MS360 may serve as a risk factor. The recently established concentric square field test indicated alterations in risk assessment as well as an increased exploratory drive and somewhat higher risk-taking behavior in adult MS360 rats, while minor effects were seen in MS15 rats. Altogether, these results demonstrate that environmental influences during the period of early life can have long-term effects on neurochemistry and behavior. Of special interest is the finding that MS altered the inherited high ethanol intake in adult ethanol-preferring AA rats.
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| 19. |
- Rosén, Annika, et al.
(författare)
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Central changes in nociceptin, dynorphin and met-enkephalin-Arg-Phe in different models of nociception
- 2000
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 857:1-2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- The newly identified neuropeptide nociceptin/orphanin FQ (NOC) was measured in different rat brain areas related to the descending anti-nociceptive pathways and compared to two opioid peptides, dynorphin B (DYN B) and Met-enkephalinArgPhe (MEAP). Two experimental models of chronic nociception, one neurogenic and one inflammatory, used in this study, reveal how different pathological conditions may influence these endogenous systems. Nerve injury is induced by ligation of the sciatic nerve and inflammation by a carrageenan injection in the gluteal muscle, 2 weeks prior to decapitation. Selected brain areas were dissected out and frozen. NOC-, DYN B- and MEAP-like immunoreactivity (LI) is determined by radioimmunoassay. Nerve injury increased the NOC-LI levels in the cortex cinguli, DYN B-LI levels in the dorsal and the ventral part of the spinal cord, whereas a decrease in the MEAP-LI levels is seen in the dorsal part of the periaqueductal grey (PAG). After inflammation, the NOC-LI levels increased in cortex cinguli, hypothalamus and in the dorsal spinal cord, whereas DYN B-LI levels increased in the dorsal part of the PAG. A general increase in MEAP-LI levels is found after inflammation in all analyzed brain areas except in hippocampus. In conclusion, increased levels of NOC-LI were found in cortex cinguli in both treatment groups and in hypothalamus and spinal cord following carrageenan treatment. The changes in the NOC-LI concentrations were not parallelled by changes in DYN B-LI and MEAP-LI, suggesting that NOC and opioid peptides elicit different reactions in the systems of nociception/antinociception.
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| 20. |
- Spetea, M, et al.
(författare)
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Alteration in endogenous systems during chronic inflammatory pain conditions
- 2002
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Ingår i: European Journal of Pharmacology. - 0014-2999 .- 1879-0712. ; 435:2-3, s. 245-252
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Tidskriftsartikel (refereegranskat)abstract
- The influence of chronic arthritic pain on two endogenous opioid peptides, dynorphin B and [Met5]enkephalin-Arg6-Phe7, and multiple opioid receptors in discrete brain, lumbar spinal cord and pituitary pools was investigated. Using radioimmunoassay and receptor binding assay, we examined the changes in regional opioid peptide levels and opioid receptor activity due to chronic inflammation in adjuvant arthritic rats. At 4 weeks post-inoculation, increased levels of immunoreactive dynorphin B and [Met5]enkephalin-Arg6-Phe7 were measured in tissues of arthritic rats compared with controls. No significant changes in mu-, delta- or kappa-opioid receptors were seen after chronic inflammation. Taken together, these results indicate that in chronic arthritis, opioid receptor changes do not follow the peptide alterations of pro-dynorphin and pro-enkephalin systems. Thus, dynamic modification and modulation of nociceptive information takes place during chronic inflammation. This supports the key role of the central nervous system in chronic inflammatory pain conditions.
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| 21. |
- Synnerstad, Ingrid, et al.
(författare)
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Intraluminal acid and gastric mucosal integrity : the importance of blood-borne bicarbonate.
- 2001
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - 0193-1857 .- 1522-1547. ; 280:1, s. G121-G129
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Tidskriftsartikel (refereegranskat)abstract
- The acid-secreting gastric mucosa resists intraluminal acid better than the nonsecreting. Here we investigated pH at the epithelial cell surface, mucosal permeability, and blood flow during intraluminal administration of acid (100 mM) in acid-stimulated and nonstimulated gastric corpus mucosae. Surface pH (H(+)-selective microelectrodes), permeability (clearance of (51)Cr-EDTA), and mucosal blood flow (laser-Doppler flowmetry) were studied in Inactin-anesthetized rats. Acid secretion was stimulated with pentagastrin (40 microg. kg(-1). h(-1)) or impromidine (500 microg. kg(-1). h(-1)), or HCO(3)(-) (5 mmol. kg(-1). h(-1)) given intravenously. Surface pH was only slightly reduced by intraluminal acid in acid secretion-stimulated or HCO(3)(-)-treated rats but was substantially lowered in nonstimulated rats. Clearance increased threefold and blood flow increased by approximately 75% in nonstimulated rats. During stimulated acid secretion or intravenous infusion of HCO(3)(-), clearance was unchanged and blood flow increased by only approximately 30% during intraluminal acid. Increased epithelial transport of HCO(3)(-) buffering the mucus gel is most probably the explanation for the acid-secreting mucosa being less vulnerable to intraluminal acid than the nonsecreting.
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| 22. |
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| 23. |
- Tan-No, Koichi, et al.
(författare)
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Antinociceptive effect produced by intracerebroventricularly administered dynorphin A is potentiated by p-hydroxymercuribenzoate or phosphoramidon in the mouse formalin test
- 2001
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 891:1-2, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- The antinociceptive effects of intracerebroventricularly (i.c.v.) administered dynorphin A, an endogenous agonist for kappa-opioid receptors, in combination with various protease inhibitors were examined using the mouse formalin test in order to clarify the nature of the proteases involved in the degradation of dynorphin A in the mouse brain. When administered i.c.v. 15 min before the injection of 2% formalin solution into the dorsal surface of a hindpaw, 1-4 nmol dynorphin A produced a dose-dependent reduction of the nociceptive behavioral response consisting of licking and biting of the injected paw during both the first (0-5 min) and second (10-30 min) phases. When co-administered with p-hydroxymercuribenzoate (PHMB), a cysteine protease inhibitor, dynorphin A at the subthreshold dose of 0.5 nmol significantly produced an antinociceptive effect during the second phase. This effect was significantly antagonized by nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by naltrindole, a selective delta-opioid receptor antagonist. At the same dose of 0.5 nmol, dynorphin A in combination with phosphoramidon, an endopeptidase 24.11 inhibitor, produced a significant antinociceptive effect during both phases. The antinociceptive effect was significantly antagonized by naltrindole, but not by nor-binaltorphimine. Phenylmethanesulfonyl fluoride (PMSF), a serine protease inhibitor, bestatin, a general aminopeptidase inhibitor, and captopril, an angiotensin-converting enzyme inhibitor, were all inactive. The degradation of dynorphin A by mouse brain extracts in vitro was significantly inhibited only by the cysteine protease inhibitors PHMB and N-ethylmaleimide, but not by PMSF, phosphoramidon, bestatin or captopril. The present results indicate that cysteine proteases as well as endopeptidase 24.11 are involved in two steps in the degradation of dynorphin A in the mouse brain, and that phosphoramidon inhibits the degradation of intermediary delta-opioid receptor active fragments enkephalins which are formed from dynorphin A.
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