Previous studies have shown that endothelin (ET) antagonizes the actions of arginine vasopressin (AVP) in the renal collecting ducts. On the other hand, the effects of AVP on ET function within the collecting ducts of the kidney have not been investigated extensively. Using isolated inner medullary collecting ducts (IMCD), we examined the possibility that a decrease in ET_B receptor mRNA accompanied AVP-induced downregulation of ET_B receptors. Binding studies revealed that overnight incubation of rat IMCD cells with AVP significantly reduced the maximal binding capacity (B_max) of ET. Activation of adenylate cyclase by forskolin decreased the total ET_B receptor density by ~42% but did not affect the density of ET_A receptors. The Rp diastereoisomer of adenosine 3',5'-cyclic monophosphothionate, Rp-cAMPS (a specific inhibitor of protein kinase A), blocked the AVP-induced reduction in ET receptor density. Using competitive PCR method, we also observed downregulation of ET_B receptor mRNA in IMCD treated with AVP. Additional studies were done with IMCD to determine whether AVP inhibited the ET-induced accumulation of cGMP. We saw a reduction in ET-induced cGMP accumulation when IMCD was incubated overnight with AVP. This inhibition of ET-induced accumulation of cGMP was blocked by Rp-cAMPS. These results suggest that AVP regulates ET_B receptor expression in IMCD.