AUTOCRINE ROLE OF ENDOTHELIN IN RAT INNER MEDULLARY COLLECTING DUCT - INHIBITION OF AVP-INDUCED CAMP ACCUMULATION

Exogenous endothelin-1 (ET-1) inhibits arginine vasopressin (AVP)-induced cAMP accumulation in the inner medullary collecting duct (IMCD). Because ET-1 is produced by and binds to specific receptors on the IMCD, the possibility exists that ET-1 is an autocrine regulator of AVP action in this nephron segment. To test this hypothesis, rat IMCD cells were grown on semipermeable membranes in the presence of rabbit anti-ET-I antiserum or nonimmune rabbit serum (NRS). AVP (10(-9) M) caused a 2.5-fold greater accumulation of cAMP in confluent IMCD monolayers preincubated in ET-1 antiserum in comparison with NRS. ET-1 (10(-8) M) inhibited the AVP-induced rise in cAMP by 65% in cells preincubated in ET-1 antiserum but had no effect in NRS-treated cells. Finally, [I-125-ET-1 (30 pM) binding was increased sixfold in IMCD preincubated in anti-ET-1 antiserum. These data indicate that ET-1 causes tonic autocrine inhibition of AVP responsiveness in the IMCD.