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-1 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, [125I]-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.
Kohan
D E
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Division of Nephrology, Veterans Affairs Medical Center, Salt Lake City, Utah.
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D016232:Endothelins / Q000187:drug effects* / Q000276:immunology; D007457:Iodine Radioisotopes; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D007457:Iodine Radioisotopes; D001127:Arginine Vasopressin; D000242:Cyclic AMP