CGMP FORMATION IN RAT ATRIAL SLICES IS LIGAND AND ENDOTHELIN RECEPTORSUBTYPE-SPECIFIC

Involvement of a cGMP pathway in signal transduction stimulated by end othelins (ETs) and sarafotoxins (SRTXs) was examined in rat atrial sli ces. These peptides activated different receptor-binding sites (ET-1 a nd SRTX-b reacted with the picomolar binding sites of the ET(A) recept or, and ET-3 and SRTX-c reacted with the nanomolar binding sites of th e ET(B) receptor) to produce cGMP. ET-1 and SRTX-b stimulated an incre ase in cGMP levels via a Ca2(+)-dependent NO pathway involving a pertu ssis toxin-insensitive protein, whereas ET-3 and SRTX-c elevated cGMP levels via a Ca2+-independent CO pathway involving a pertussis toxin-s ensitive G protein. These results can best be explained in terms of fo rmation of different ligand-receptor-G-protein complexes. The ligands had no effect on ventricular slices, indicating that these signal tran sduction mechanisms are unique to the atria.