Autocrine role of endothelin in rat IMCD: inhibition of AVP-induced cAMP accumulation.
Exogenous endothelin-1 (ET-1) inhibits arginine vasopressin (AVP)-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in the inner medullary collecting duct (IMCD). Since 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 grown on semipermeable membranes were exposed to rabbit anti-ET antisera or nonimmune rabbit sera (NRS). AVP (10(-9)M) caused a significantly greater accumulation of cAMP in confluent IMCD monolayers preincubated in ET-1 antisera compared with 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-treated cells. Finally, 125I-ET-1 (30 pM) binding was increased sixfold in IMCD preincubated in anti-ET-1 antisera. These data indicate that ET causes tonic autocrine inhibition of AVP responsiveness in the IMCD.
Kohan
D E
DE
Division of Nephrology, Veterans Affairs Medical Center, Salt Lake City, Utah.
Hughes
A K
AK
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016232:Endothelins / Q000276:immunology / Q000502:physiology*; D007106:Immune Sera / Q000276:immunology; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism
D016232:Endothelins; D007106:Immune Sera; D017466:Receptors, Endothelin; D001127:Arginine Vasopressin; D000242:Cyclic AMP