Endothelin-1 stimulates phosphoinositide hydrolysis in the rat pineal gland.
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.
Garrido
M D
MD
School of Pharmacy, Department of Biological Science, Universidad Central de Venezuela, Caracas, Venezuela.
Israel
A
A
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
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