| 1. |
- Blay, Pilar, et al.
(författare)
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An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges
- 1994
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 662:1-2, s. 148-154
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Tidskriftsartikel (refereegranskat)abstract
- Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges.
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| 2. |
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| 3. |
- Lindvall-Axelsson, Maria, et al.
(författare)
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Inhibition of cerebrospinal fluid formation by omeprazole
- 1992
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 115:3, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.
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| 4. |
- Nilsson, Christer, et al.
(författare)
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Distribution of peptidergic nerves in the choroid plexus, focusing on coexistence of neuropeptide Y, vasoactive intestinal polypeptide and peptide histidine isoleucine
- 1990
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 27:1, s. 11-26
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Tidskriftsartikel (refereegranskat)abstract
- Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.
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| 5. |
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| 6. |
- Nilsson, Christer, et al.
(författare)
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Epithelial cells purified from choroid plexus have receptors for vasoactive intestinal polypeptide
- 1991
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Ingår i: Brain Research. - 1872-6240. ; 542:2, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- Using the choroid plexus from pig a method has been developed to purify the epithelial cells from the underlying vascularized connective tissue stroma. An epithelial cell fraction was obtained that showed a purity of at least 95%, as determined by light microscopic analysis. The epithelial cells were investigated for the presence of binding sites for the neurotransmitter peptide, vasoactive intestinal polypeptide (VIP). Suspensions of epithelial cells were found to have high affinity binding sites for 125I-labelled VIP, with maximum binding obtained after 30 min incubation at 20 degrees C with a concentration of 50 micrograms cell protein per sample. Competition experiments with displacement of [125I]VIP binding by increasing concentrations of unlabeled VIP indicated the presence of a single class of binding sites with a Kd of 3 nM and a binding capacity of 970 pmol/g cell protein. Cross-linking of [125I]VIP to epithelial cells with disuccinimido dithiobis (propionate) (DSP), followed by SDS-polyacrylamide gel electrophoresis, demonstrated binding to a single 55 kD protein. The receptor was highly specific for VIP as binding was only inhibited in the presence of high concentrations of the related peptides helodermin, growth hormone-releasing factor, secretin, and peptide histidine isoleucine. This is the first demonstration of VIP-binding to choroid plexus epithelial cells.
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| 7. |
- Nilsson, Christer, et al.
(författare)
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Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system
- 1992
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Ingår i: Brain research. Brain research reviews. ; 17:2, s. 109-138
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Forskningsöversikt (refereegranskat)abstract
- The CSF is often regarded as merely a mechanical support for the brain, as well as an unspecific sink for waste products from the CNS. New methodology in receptor autoradiography, immunohistochemistry and molecular biology has revealed the presence of many different neuroendocrine substances or their corresponding receptors in the main CSF-forming structure, the choroid plexus. Both older research on the sympathetic nerves and recent studies of peptide neurotransmitters in the choroid plexus support a neurogenic regulation of choroid plexus CSF production and other transport functions. Among the endocrine substances present in blood and CSF, 5-HT, ANP, vasopressin and the IGFs have high receptor concentrations in the choroid plexus and have been shown to influence choroid plexus function. Finally, the choroid plexus produces the growth factor IGF-II and a number of transport proteins, most importantly transthyretin, that might regulate hormone transport from blood to brain. These studies suggest that the choroid plexus-CSF system could constitute an important pathway for neuroendocrine signalling in the brain, although clearcut evidence for such a role is still largely lacking.
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| 8. |
- Nilsson, Christer, et al.
(författare)
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The neuropeptides vasoactive intestinal polypeptide, peptide histidine isoleucine and neuropeptide Y modulate [3H]noradrenaline release from sympathetic nerves in the choroid plexus
- 1990
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 181:3, s. 247-252
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Tidskriftsartikel (refereegranskat)abstract
- The neurotransmitter peptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and neuropeptide Y (NPY) are located in nerve fibers supplying the pig choroid plexus, which receives an abundant sympathetic innervation. We characterized the release of [3H]noradrenaline ([3H]NA) from this tissue elicited by electrical field stimulation and studied the effects of the above-mentioned peptides on this release. The release of [3H]NA was found to be almost exclusively of neurogenic origin, despite there being a marked non-neuronal uptake of [3H]NA into the epithelium of the choroid plexus. NPY significantly decreased the release of [3H]NA by approximately 10% while VIP and PHI enhanced release by up to 25 and 35%, respectively, indicating a possible synergistic role of the two latter peptides and NA in the choroid plexus.
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| 9. |
- Owman, Christer, et al.
(författare)
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Cloning of cDNA encoding a putative chemoattractant receptor
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 1089-8646 .- 0888-7543. ; 37:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Based on polymerase chain reaction (PCR) utilizing degenerate primers directed to the second and sixth transmembrane domains of several G-protein-coupled neurotransmitter receptors and screening of a human B-lymphoblast cDNA library, we isolated a cDNA whose predicted amino acid sequence shows considerable homology with human chemoattractant receptors, e.g., 30% overall identity with the C5a anaphylatoxin receptors. The coding region consists of 1056 bp corresponding to 352 amino acid residues and giving an approximate molecular weight of 43 kDa. Northern blot analysis showed hybridizing transcripts in spleen, thymus, and lymph nodes, as well as in bone marrow and peripheral blood leukocytes. Message was also found in lymphoid tumor cell lines. Chromosome mapping with FISH/DAPI technique showed the corresponding gene to reside on human chromosome 14q11.2-q12. In accordance with the Genome Database Nomenclature the receptor was designated CMKRL1 ("chemoattractant receptor-like 1"). Stably transfected mammalian cells (CHO cells and LVIP2.0Zc reporter cells) expressing high levels of corresponding receptor RNA were analyzed for changes in cAMP concentration and cellular calcium fluxes. Chemokines tested to date (GRO-a, MCP-1, MCP-3, MIP-1a, MIP-1b, C5a, RANTES, and LTB4) have failed to elicit any reproducible response. Although the ligand for CMKRL1 could thus not be identified among chemotactic peptides, the high expression in lymphoid cells and tissues suggests that the receptor may function in the regulation of the inflammatory system.
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| 10. |
- Owman, Christer, et al.
(författare)
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Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues
- 1996
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 228:2, s. 285-292
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Tidskriftsartikel (refereegranskat)abstract
- Using PCR with degenerate primers and screening of a human B-cell lymphoblast cDNA library, a full-length cDNA encoding a 375-amino-acid protein was isolated. It contains seven regions of hydrophobic amino acids probably representing membrane-spanning domains of a novel heptahelix receptor, tentatively named CMKRL2. It shows nearly 30% overall identity with the high-affinity IL8 receptor and similar degree of homology with other chemoattractant receptors, including the "fusin" coreceptors for HIV1. Measurements of various transduction pathways following application of a panel of chemokines to transfected cells failed to evoke any reproducible response. Although the natural ligand for CMKRL2 could, thus, not be identified, receptor expression in spleen and lymph nodes as well as in Burkitt's lymphoma (irrespective of EBV status) supports a functional role in activated B-cells. Receptor message was ubiquitously distributed in normal peripheral tissues and CNS, suggesting that CMKRL2 is expressed in widespread cell populations, such as macrophages and neuroglia.
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