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Endothelin Receptors on Cultured Fetal Rat Diencephalic Glia
Author(s) -
Levin Ellis R.,
Frank Harrison J. L.,
Pedram Ali
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09768.x
Subject(s) - receptor , cycloheximide , medicine , endocrinology , endothelins , biology , endothelin receptor , astrocyte , neuroglia , protein kinase c , endothelin 3 , microbiology and biotechnology , biochemistry , signal transduction , protein biosynthesis , central nervous system
The recently described family of proteins, the endothelins, are produced in neurons and bind to extravascular sites in the CNS. To characterize these receptors, we carried out studies on cultures of fetal rat diencephalic glia. Scatchard analysis of saturation binding studies was done for astrocytes (>95% glial fibrillary acidic protein positive). For endothelin 3 (ET‐3) and ET‐1, respectively, a single receptor class of K D 0.41 ± 0.05 and 0.62 ± 0.04 n M and a receptor density of 42 ± 0.8 and 58 ± 1.1 fmol/mg of glial protein was found. Bound and cross‐linked 125 I‐ET‐3 or ET‐1 showed a single predominant receptor band at M, 52,000 on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis; a minor band at 50,000 was also seen. At concentrations equal to the receptor K D , the major brain form of ET, ET‐3, stimulated a nearly 200% increase in the incorporation of tritiated thymidine into glia. ET‐3 and ET‐1 significantly impaired the ability of atrial natriuretic peptide (ANP) to generate cyclic GMP, and isoproterenol to generate cyclic AMP. The ability of ET to inhibit ANP‐induced cyclic GMP generation was reversed by cycloheximide and actinomycin‐D, whereas the inhibition of isoproterenol‐induced cyclic AMP generation was partially and significantly blocked by inhibitors of calcium influx, protein kinase C action, or G protein activation, as well. Astrocytes from this part of the brain are a potential target cell for endothelin, assuming these findings are present in vivo. This neuropeptide may serve as a growth stimulator for astrocytes and modulator of the actions of catecholamines or ANP on glia by inhibiting second messenger generation.