Cerebellar neurons and glia respond differentially to endothelins and sarafotoxin S6b.
Endothelins (ETs) and sarafotoxin-S6b belong to a family of extremely potent vasoconstrictors which may also have a role as neuropeptides or neuromodulators in the central nervous system (CNS). We show, using single cell dynamic video imaging of intracellular free calcium ions ([Ca2+]i), that binding of ET to its receptors modulates [Ca2+]i of neurons as well as glial cells in primary cultures of rat cerebellum. At least two receptor subtypes, differing in both their ligand specificity and distribution, appear to be involved in the action of ETs and sarafotoxin S6b on these cells. One of these receptors may be a previously undescribed neuronal form of ET receptor. This is the first demonstration of a direct effect of ETs on neurons as well as glia in the CNS. These data support a possible role for ET as a neurotransmitter or neuromodulator in the CNS.
Morton
A J
AJ
Department of Pharmacology, University of Cambridge, UK.
Davenport
A P
AP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004622:Embryo, Mammalian; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017466:Receptors, Endothelin / Q000502:physiology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D002118:Calcium