RT Journal Article SR Electronic T1 RES-701-1, a novel, potent, endothelin type B receptor-selective antagonist of microbial origin. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 724 OP 730 VO 45 IS 4 A1 T Tanaka A1 E Tsukuda A1 M Nozawa A1 H Nonaka A1 T Ohno A1 H Kase A1 K Yamada A1 Y Matsuda YR 1994 UL http://molpharm.aspetjournals.org/content/45/4/724.abstract AB The unique cyclic peptide designated RES-701-1 blocked the binding of 125I-labeled endothelin (ET)-1 to bovine cerebellar membranes. ETB receptors are predominant in bovine cerebellum. However, in bovine lung membranes, where both ETA and ETB receptors are expressed, RES-701-1 inhibited 125I-ET-1 binding by up to 70%; RES-701-1, in the presence of the ETA-selective antagonist BQ-123 at 1 microM, displaced 125I-ET-1 binding completely. With membranes from transfected Chinese hamster ovary cells expressing the human ETA or ETB receptors, RES-701-1 inhibited 125I-ET-1 binding to the ETB receptor with an IC50 value of 10 nM but had no effect on 125I-ET-1 binding to the ETA receptor. Thus, RES-701-1 is highly specific for the ETB receptor; it has no effect on a number of other receptors. RES-701-1 selectively inhibited the ET-1-induced increase in intracellular Ca2+ concentration in COS-7 cells expressing the ETB receptor but did not inhibit the Ca2+ transient in ETA-expressing cells. When injected intravenously (250 nmol/kg) into anesthetized rats, RES-701-1 abolished the initial depressor response to ET-1 but enhanced the subsequent pressor response. These results suggest that RES-701-1 is a potent and specific antagonist for the ETB receptor and that RES-701-1 will be a powerful tool for understanding the physiological roles of this receptor.