| 1. |
- Sharma, P, et al.
(författare)
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Cloning and functional expression of the guinea pig neuropeptide Y Y2 receptor
- 1998
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115. ; 75-76, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Five neuropeptide Y (NPY) receptor subtypes have been cloned in mammals. The degree of sequence conservation differs considerably between subtypes as well as between evolutionary lineages. To shed further light on this, we have cloned the five NPY receptors in the guinea pig. Here, we report the cloning of the guinea pig Y2 receptor. The Y2 receptor is generally highly conserved, with 90-95% identity between different orders of mammals, including the guinea pig. The guinea pig receptor has a divergent cytoplasmic tail, indicating possible differences in regulation of signalling and/or down regulation. COS-7 cells transiently transfected with the gpY2 receptor show saturable 125I-PYY binding with a Kd = 6 pM. In displacement experiments, the gpY2 receptor was similar to the human and rat receptors with the following rank order of potencies: pNPY > pPYY > pNPY13-36 = pNPY22-36 > [Leu31Pro34]NPY > BIBP3226. Thus, the guinea pig Y2 receptor is well conserved in comparison with human and rat with regard to both amino acid sequence and pharmacological profile.
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| 14. |
- Gunnarsson, Tove, et al.
(författare)
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Cholecystokinin peptides in cerebrospinal fluid : a study in healthy male subjects
- 1997
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 68:1, s. 57-61
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Tidskriftsartikel (refereegranskat)abstract
- The clinical reliability of measuring cholecystokinin (CCK) peptides in the cerebrospinal fluid (CSF) has not been fully elucidated. Therefore, we have assayed CCK-8S and CCK-4 in CSF obtained from 14 healthy male subjects, lumbar-punctured at the L4–5 level following a strictly standardised procedure. CSF concentrations of free CCK-8S and free CCK-4 were used as dependent variables while age, height, body weight, atmospheric pressure and some other factors served as independent variables. It was shown that the CCK-8S ratio between the second (7–12 ml) and first (0–6 ml) CSF fractions, correlated significantly with the atmospheric pressure at the time of puncture. Neither CCK-8S nor CCK-4 displayed concentration gradients in CSF. The CCK-4 levels, expressed as pmol l−1 in the total amount of CSF were found to be positively correlated with the neuraxis distance in the lying position and negatively with the neuraxis distance in the sitting position. Furthermore, CCK-4, expressed as pmol l−1 per min of tapping-time (pmol l−1 min−1), showed a negative correlation with storage time, presumably mirroring a proteolytic process. CCK-8S and CCK-4 intercorrelated positively independently of whether expressed as pmol l−1 or pmol l−1 min−1. In conclusion, the results of this exploratory study indicate that the neuraxis distance (in the sitting and lying positions) and storage-time have to be accounted for when interpreting data on CSF levels of CCK-4. Attention has to be paid to the potential influence of atmospheric pressure on the concentration ratio of CCK-8S.
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| 26. |
- Nässel, Dick, et al.
(författare)
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Evidence that locustatachykinin I is involved in release of adipokinetic hormone from locust corpora cardiaca
- 1995
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 57:3, s. 297-310
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Tidskriftsartikel (refereegranskat)abstract
- The glandular cells of the corpus cardiacum of the locust Locusta migratoria, known to synthesize and release adipokinetic hormones (AKH), are contacted by axons immunoreactive to an antiserum raised against the locust neuropeptide locustatachykinin I (LomTK I). Electron-microscopical immunocytochemistry reveals LomTK immunoreactive axon terminals, containing granular vesicles, in close contact with the glandular cells cells. Release of AKH I from isolated corpora cardiaca of the locust has been monitored in an in vitro system where the amount of AKH I released into the incubation saline is determined by reversed phase high performance liquid chromatography with fluorometric detection. We could show that LomTK I induces release of AKH from corpora cardiaca in a dose-dependent manner when tested in a range of 10-200 microM. This is thus the first clear demonstration of a substance inducing release of AKH, correlated with the presence of the substance in fibers innervating the AKH-synthesizing glandular cells, in the insect corpora cardiaca.
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| 27. |
- Portela-Gomes, Guida M., et al.
(författare)
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Co-localization of chromogranins and neuroendocrine hormones in the human gastrointestinal mucosa
- 1996
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 64:1, s. 154-154
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Recension (refereegranskat)abstract
- Co-localization of chromogranin (Cg) A, B and C has been studied in different neuroendocrine cell types in histologically normal mucosa from human gastrointestinal (GI) tract (corpus, antrum, duodenum, ileum and colon). Single, double and triple immunofluorescence stains were used, including appropriate controls. The results showed that whereas CgA cells predominated in all GI-regions, CgB cells were numerous in antrum, few in duodenum (only villi), and almost non-existent in corpus, ileum and colon. CgC cells were sparse in antrum and duodenum (only crypts). Concerning co-localization, gastrin cells harboured CgA and B, some also CgC. All EC cells displayed CgA-immunoreactivity. The EC cells localized in the luminal 23 of the antral mucosa and those in the duodenal villi also contained CgB. Occasionally the EC cells in the duodenal crypts displayed CgC. Almost all cells showing immunoreaction to enteroglucagon/PYY, secretin, neurotensin, or GIP were positive for CgA. Somatostatin cells were with few exceptions CgA-negative, and displayed neither CgB nor C immunoreactivity. CCK cells, indirectly identified, were negative for CgB and C, probably also for CgA.Regarding intracellular localization, CgA and C were seen closer to the basal cell regions, whereas CgB was found more diffusely spread throughout the cytoplasm. This difference in localization between chromogranins suggests that not all secretory granules contain CgA or that CgB may appear in a non-granular form. The results confirm previous findings that CgA occurs in most neuroendocrine cell types of the GI-tract. In most gastrin cells there were two sets of chromogranins, CgA and B, a minority all three chromogranins. All EC cells were CgA immunoreactive, a minority also contained CgB (antrum + duodenal villi) or CgC (duodenal crypts), but not both. All CCK cells seem to be devoid of chromogranins. With few exceptions the same was true of the somatostatin cells. An interesting question posed by the present study is why the chromogranins occur in varying extent and composition in the different cell types.
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| 29. |
- Sandin, Johan, et al.
(författare)
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Metabolism of beta-endorphin in plasma studied by liquid chromatography-electrospray ionization mass spectrometry
- 1998
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 73:1, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Degradation of synthetic human beta-endorphin by a human plasma proteinase was studied with high-performance liquid chromatography in combination with mass spectrometry. The peptide was metabolized at a rate of 25 pmol/min to the major fragments beta-endorphin (1-19) and (20-31), the latter reported as a potent inhibitor of morphine- and beta-endorphin-induced analgesia in mice. The proteinase responsible for this process was classified as a metal-dependent serine proteinase and was effectively inactivated by phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Identification of the products formed during the enzymatic reaction was performed by liquid chromatography on-line with electrospray mass spectrometry, using a reversed-phase or a novel size-exclusion column capable of separating molecules between 0.1-7 kilodaltons. Peptide sequences were verified by tandem mass spectrometry experiments. The conversion of beta-endorphin may have physiological implications in the mechanism of pain. The obtained data suggest that several precautions should be considered during recovery and measurement of beta-endorphin in plasma by immunological techniques. The applied strategy may also be useful for studying metabolism of various peptidergic compounds with potential pharmacological significance.
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| 31. |
- Stridsberg, Mats, et al.
(författare)
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Islet amyloid polypeptide (IAPP) in patients with neuroendocrine tumours
- 1995
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 55:2, s. 119-131
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Tidskriftsartikel (refereegranskat)abstract
- Although IAPP was first discovered and isolated from amyloid deposits in an endocrine pancreatic tumour (EPT), surprisingly few reports have investigated the potential use of IAPP as a marker for neuroendocrine tumour growth. In this study we present results from plasma measurements of IAPP in 102 patients with neuroendocrine tumours. Four of 35 patients (11%) with midgut carcinoid tumours, but none of the patients (4 and 5, respectively) with lung carcinoids or with rectal carcinoids displayed elevated plasma levels of IAPP. Five of 31 patients (16%) with sporadic EPT and 3 of 27 patients (11%) with EPT and multiple endocrine neoplasia type 1 syndrome disclosed elevated IAPP levels. Within the different syndromes, 1/11 individuals with insulinoma, 2/16 with gastrinoma, 0/2 with glucagonoma, 0/3 with VIPoma and 5/26 with non-functioning tumours showed elevated plasma levels of IAPP. In two patients, the plasma IAPP levels were extremely elevated. These patients also exhibited altered glucose homeostasis. In response to a standardised mixed meal test, IAPP increased in parallel to the insulin, pancreatic polypeptide, gastrin and glucose responses. In MEN1 patients with hypercalcaemia due to increased secretion of parathyroid hormone, the plasma levels of IAPP were significantly higher before than after surgical removal of the parathyroid adenomas. However in normocalcaemic patients, no correlation between the blood calcium and plasma IAPP levels was found. Immunocytochemical staining of tumour tissue showed that 9/13 (69%) of insulin producing tumours, 4/14 (29%) of non-functioning tumours and 1/9 (11%) of gastrin producing tumours were IAPP immunoreactive. Amyloid deposits were always IAPP immunoreactive. In conclusion, increased circulating levels of IAPP occurred in 12% of 102 patients with neuroendocrine tumours. In 2 patients with extremely elevated plasma levels of IAPP, effects on glucose homeostasis were recorded. Thus, IAPP may be useful as an additional marker for neuroendocrine tumour growth in selected cases.
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| 42. |
- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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Chronic intracerebroventricular administration of beta-endorphin augments natural killer cell cytotoxicity in rats.
- 1996
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Ingår i: Regulatory peptides. - 0167-0115. ; 62:2-3, s. 113-8
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the effect of chronic intracerebroventricular (i.c.v.) infusion of different opioid peptides on natural killer (NK) cell mediated cytotoxicity in vivo in the spontaneously hypertensive rat (SHR). The in vivo NK cell activity was measured as the clearance of 51Cr-labelled YAC-l lymphoma cells from the lung tissues. Further, the phenotype of lymphocytes in spleen and peripheral blood was analysed by flow cytometry (FACS). All opioid drugs were administered i.c.v. for 6 days with osmotic minipumps releasing 1.0 microliter/h. beta-Endorphin (10 or 20 micrograms/rat per day) significantly increased NK cell cytotoxicity in vivo. The opioid receptor antagonist naloxone (10 mg/kg, i.p.) given immediately before the injection of YAC-lymphoma cells, completely abolished the effects of i.c.v. administered beta-endorphin. Corresponding doses of beta-endorphin administered subcutaneously (s.c.) with minipumps for 6 days did not significantly affect NK cell cytotoxicity. Neither Leu- or Met-enkephalin (20 micrograms/rat per day) nor dynorphin (20 micrograms/rat per day) administered i.c.v. had any significant effects on NK cell activity. In beta-endorphin treated SHR, the percentage of cells with NK cell phenotype (OX52+/CD5-) in peripheral blood was not significantly different from that of controls, while the percentage of cells with T cell phenotype (CD5+/OX52-) was significantly decreased. The percentage of splenic NK cells (OX52+/CD5-) and T cells (CD5+/OX52-) was also unchanged by beta-endorphin treatment i.c.v. These results suggest that of the opioid peptides administered i.c.v., only beta-endorphin augments in vivo NK cell mediated cytotoxicity. We thus conclude that these effects most probably are centrally and opioid receptor mediated effects, since beta-endorphin in the same dose administered peripherally does not influence in vivo NK cell cytotoxicity.
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| 44. |
- Kölby, Lars, 1963, et al.
(författare)
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Altered influence of CCK-B/gastrin receptors on HDC expression in ECL cells after neoplastic transformation.
- 1999
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Ingår i: Regulatory peptides. - 0167-0115. ; 85:2-3, s. 115-23
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Tidskriftsartikel (refereegranskat)abstract
- Gastrin is one of the main factors controlling enterochromaffin-like (ECL) cell endocrine function and growth. Long-standing hypergastrinemia may give rise to ECL cell carcinoids in the gastric corpus in man and in experimental models. We have analysed the expression and function of CCK-B/gastrin receptors in normal ECL cells and in ECL cell tumours (gastric carcinoids) of the African rodent Mastomys natalensis. Hypergastrinemia induced by short-term (5 days) histamine2-receptor blockade (loxtidine) resulted in increased histidine decarboxylase (HDC) mRNA expression in the gastric oxyntic mucosa. This increase was significantly and dose-dependently reversed by selective CCK-B/gastrin receptor blockade (YM022). Long-term (12 months) hypergastrinemia, induced by histamine2-receptor blockade, gave rise to ECL cell carcinoids in the gastric oxyntic mucosa. CCK-B/gastrin receptor mRNA was only slightly elevated while HDC mRNA expression was eight-fold elevated in ECL cell carcinoids and was not influenced by CCK-B/gastrin receptor blockade. Thus CCK-B/gastrin receptor blockade of hypergastrinemic animals reduces the HDC mRNA expression in normal mucosa but not in ECL cell carcinoids. These results demonstrate that HDC mRNA expression in neoplastic ECL cells is not controlled by CCK-B/gastrin receptors.
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| 45. |
- Thorsell, Annika, et al.
(författare)
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Cationic lipid-mediated delivery and expression of prepro-neuropeptide Y cDNA after intraventricular administration in rat : feasibility and limitations.
- 1996
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 61:3, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- The utility of in vivo lipofection for delivery and expression of a neuropeptide gene in the adult rat brain was explored. Prepro-neuropeptide Y (NPY) cDNA was cloned into the episomal eucaryotic expression vector pCEP4. This construct was complexed to lipofectamine or lipofectin. Complexed DNA was injected into the lateral ventricles of adult rats. Brains were removed for analysis following various time intervals. Polymerase chain reaction (PCR) reactions were designed for specific detection of endogenous and vector derived NPY sequence, respectively. PCR of DNA preparations from 5 major brain regions (frontal and parietal cortex, striatum, hypothalamus, brain stem) demonstrated presence of vector DNA up to 1 month (longest interval studied) in all brain regions. Reverse-transcription (RT-) PCR of DNase treated RNA-preparations from brain tissue demonstrated presence of both vector-derived and endogenous NPY mRNA in treated animals, while only endogenous mRNA was detected in controls. In situ hybridization histochemistry indicated scattered patches of vector uptake into tissue in the vicinity of the CSF compartment, but not into deeper located structures. Weight gain was not affected, indicating that the expression levels achieved may not be sufficient to play a functional role, and/or may need to be targeted to specific brain areas. These findings suggest a potential for cationic lipid mediated gene transfer in the brain as an experimental tool and as a possible future therapeutic principle, but also indicate the need for optimization of delivery strategies in order to achieve functionally relevant expression levels.
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| 46. |
- Wängberg, Bo, 1953, et al.
(författare)
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Are enterochromaffinlike cell tumours reversible? An experimental study on gastric carcinoids induced in Mastomys by histamine2-receptor blockade.
- 1995
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Ingår i: Regulatory peptides. - 0167-0115. ; 56:1, s. 19-33
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Tidskriftsartikel (refereegranskat)abstract
- A rapid induction of enterochromaffinlike (ECL) cell tumours has been shown in Praomys (Mastomys) natalensis subjected to histamine2-receptor blockade. In the present study the reversibility of ECL cell proliferation induced by acid inhibition was investigated. Short-term treatment (8 weeks) with the histamine2-receptor antagonist loxtidine caused a moderate hypergastrinemia, accompanied by a minor increase in histamine contents and a 2-fold increased volume density of the endocrine cells in gastric oxyntic mucosa. Eight weeks after withdrawal of treatment the volume density of endocrine cells was normalised as were the tissue levels of histamine, indicating a total reversibility of ECL cell hyperplasia. Long-term treatment (24 weeks) caused severe changes in the endocrine cell population of the oxyntic mucosa with neoplasia (5/21), dysplasia (11/21) and nodular hyperplasia (5/21). The endocrine cell density increased twofold and tissue histamine levels fourfold. 24 weeks after cessation of treatment, the endocrine cell density had decreased to 136% of controls, while histamine concentrations were normalised. The frequency of invasive carcinoids after recovery (4/23) differed only slightly from that seen after treatment for 24 weeks (5/21). Dysplastic lesions were only seen in 1/23 and hyperplastic lesions were of less severe type after recovery. The results demonstrate that ECL cell hyperplasia and dysplasia, induced by acid inhibition, are reversible after cessation of treatment. However, ECL cell tumours did not disappear, within the given observation period. One may therefore speculate that ECL cell proliferation is no longer reversible once the neoplastic (transformed) phenotype has developed.
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