cGMP formation in rat atrial slices is ligand and endothelin receptor subtype specific.
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 picomolar binding sites of the ET(A) receptor, and ET-3 and SRTX-c reacted with the nanomolar binding sites of the ET(B) 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.
Shraga-Levine
Z
Z
Laboratory of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Sokolovsky
M
M
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017466:Receptors, Endothelin / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008024:Ligands; D010455:Peptides; D017466:Receptors, Endothelin; D014757:Viper Venoms; C089502:sarafotoxin-c; C057354:sarafotoxins s6; D009569:Nitric Oxide; D006152:Cyclic GMP