Endothelin-3 stimulates phosphoinositide hydrolysis in the subfornical organ and median eminence of the rat brain.
The effect of Endothelin-3 on phosphoinositide turnover was studied in two brain structures, the subfornical organ and median eminence. ET-3 increased inositol monophosphate accumulation in the range 1 nM to 2 microM. Basal and stimulated InsP1 accumulation increased linearly during 1 h. The PI response elicited by ET-3 was dependent on the presence of extracellular Ca++. Removal of extracellular Ca++ or addition of Cd++ resulted in a marked decrease in ET-3-stimulated InsP1 accumulation. On the contrary, phosphoinositide hydrolysis was not changed by the calcium channel blockers nifedipine or amlodipine; however, it was decreased by amiloride, a Na+/H+ antiporter or Na+/Ca++ exchange blocker. ET-3 induced PI breakdown was inhibited in, a dose-dependent manner, by neomycin, an inhibitor of phospholipase C. These findings further support the hypothesis that stimulation of PI turnover constitutes one of the signalling pathways of ET-3 in the central nervous system, possibly through the stimulation of a specific receptor coupled to phospholipase C.
Garrido
M R
MR
School of Pharmacy, Department of Basic Biological Sciences, Universidad Central de Venezuela, Caracas.
Israel
A
A
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D008473:Median Eminence / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013356:Subfornical Organ / Q000378:metabolism*
D016232:Endothelins; D010716:Phosphatidylinositols; D000584:Amiloride; D002118:Calcium