title: Endothelin-1 stimulates phosphoinositide hydrolysis in the rat pineal gland.
abstract: The presence of functional endothelin receptors and their signal transduction mechanism has not been determined so far in the pineal gland. We examined the effect of endothelin-1 (ET-1) on phosphoinositide turnover in whole pineal gland. Endothelin-1 increased monophosphate accumulation in a dose-dependent manner. The phosphoinositide (PI) response elicited by ET-1 was dependent on the presence of extracellular Ca (++) since its chelation resulted in a marked decrease in ET-1-stimulated InsP(1) accumulation. On the contrary, phosphoinositide hydrolysis was not changed by the calcium blocker amlodipine. ET-1 induced PI breakdown was inhibited by neomycin, an inhibitor of phospholipase C. However, mastoparan 7, a G protein activator via Gi/Go s timulation, did not alter ET-1-induced InsP(1) accumulation. Our data indicate that stimulation of PI turnover constitutes one of the signaling pathways of ET in rat pineal gland through the stimulation of a receptor-coupled phospholipase C. And they demonstrate, for the first time, the presence of functional binding sites for endothelin in the pineal gland.
authors.affiliation: School of Pharmacy, Department of Biological Science, Universidad Central de Venezuela, Caracas, Venezuela.
authors.forename: M D
authors.initials: MD
authors.lastname: Garrido
authors.forename: A
authors.initials: A
authors.lastname: Israel
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D010455:Peptides; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010716:Phosphatidylinositols; D017466:Receptors, Endothelin; D014862:Wasp Venoms; D017311:Amlodipine; D004533:Egtazic Acid; C037500:mastoparan; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D009355:Neomycin; D002118:Calcium