LIGAND-SPECIFIC STIMULATION INHIBITION OF CAMP FORMATION BY A NOVEL ENDOTHELIN RECEPTOR SUBTYPE/

The possible involvement of a cAMP pathway in endothelin (ET) signal t ransduction was explored using rat atrial slices. We show that ET-1 in duces both stimulation and inhibition of cAMP formation, depending on its concentration. Unexpectedly, the effects of ET-3 and of sarafotoxi ns b and c (SRTX-b and SRTX-c) on this pathway differ from that of ET- 1. Moreover, we show that the ET-1-induced formation of cAMP results f rom catecholamine release in a process mediated by a Ca2+ channel coup led to a pertussis toxin sensitive G-protein. It is concluded that thi s pathway is mediated by a new ET(A) receptor subtype (probably presyn aptic), for which ET-1 is an agonist and ET-3, SRTX-b, and SRTX-c are antagonists.