title: Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells.
abstract: We have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice as well as primary and continuous cell cultures. A glial role is favored by several observations: (i) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C6 glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C6 glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: M W
authors.initials: MW
authors.lastname: MacCumber
authors.forename: C A
authors.initials: CA
authors.lastname: Ross
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D016232:Endothelins; D004730:Endothelium, Vascular; D005910:Glioma; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology*; D017466:Receptors, Endothelin
chemical_list: D016232:Endothelins; D007295:Inositol Phosphates; D010455:Peptides; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin