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 subfomical organ and median eminence. ET-3 increased inositol monophosphate accumulation in the range 1 nM to 2 mu M. Basal and stimulated InsP(1) 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.