cGMP Formation in Rat Atrial Slices Is Ligand and Endothelin Receptor Subtype Specific

Abstract Involvement of a cGMP pathway in signal transduction stimulated by endothelins (ETs) and sarafotoxins (SRTXs) was examined in rat atrial slices. These peptides activated different receptor-binding sites (ET-1 and SRTX-b reacted with the picomolar binding sites of the ETA receptor, and ET-3 and SRTX-c reacted with the nanomolar binding sites of the ETB receptor) to produce cGMP. ET-1 and SRTX-b stimulated an increase in cGMP levels via a Ca2+-dependent NO pathway involving a pertussis toxin–insensitive G protein, whereas ET-3 and SRTX-c elevated cGMP levels via a Ca2+-independent CO pathway involving a pertussis toxin–sensitive G protein. These results can best be explained in terms of formation of different ligand-receptor–G-protein complexes. The ligands had no effect on ventricular slices, indicating that these signal transduction mechanisms are unique to the atria.