AUTOCRINE ROLE OF ENDOTHELIN IN RAT IMCD - INHIBITION OF AVP-INDUCED CAMP ACCUMULATION

Exogenous endothelin-1 (ET-1) inhibits arginine vasopressin (AVP)-indu ced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in the in ner medullary collecting duct (IMCD). Since ET-1 is produced by, and b inds to specific receptors on, the IMCD, the possibility exists that E T-1 is an autocrine regulator of AVP action in this nephron segment. T o test this hypothesis, rat IMCD cells grown on semipermeable membrane s were exposed to rabbit anti-ET antisera or nonimmune rabbit sera (NR S). AVP (10(-9) M) caused a significantly greater accumulation of cAMP in confluent IMCD monolayers preincubated in ET-1 antisera compared w ith NRS. ET-1 (10(-8) M) inhibited the AVP-induced rise in cAMP by 65% in cells preincubated in ET-1 antisera, but had no effect in NRS-trea ted cells. Finally, I-125-ET-1 (30 pM) binding was increased sixfold i n IMCD preincubated in anti-ET-1 antisera. These data indicate that ET causes tonic autocrine inhibition of AVP responsiveness in the IMCD.