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  • Title: Autocrine role of endothelin in rat IMCD: inhibition of AVP-induced cAMP accumulation.
    Author: Kohan DE, Hughes AK.
    Journal: Am J Physiol; 1993 Jul; 265(1 Pt 2):F126-9. PubMed ID: 8393621.
    Abstract:
    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.
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