Ligand-specific stimulation/inhibition of cAMP formation by a novel endothelin receptor subtype.
The possible involvement of a cAMP pathway in endothelin (ET) signal transduction was explored using rat atrial slices. We show that ET-1 induces both stimulation and inhibition of cAMP formation, depending on its concentration. Unexpectedly, the effects of ET-3 and of sarafotoxins 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 from catecholamine release in a process mediated by a Ca2+ channel coupled to a pertussis toxin sensitive G-protein. It is concluded that this pathway is mediated by a new ETA receptor subtype (probably presynaptic), for which ET-1 is an agonist and ET-3, SRTX-b, and SRTX-c are antagonists.
Sokolovsky
M
M
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Shraga-Levine
Z
Z
Galron
R
R
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010455:Peptides / Q000378:metabolism; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014757:Viper Venoms / Q000378:metabolism
D015220:Calcium Channels; D002395:Catecholamines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008024:Ligands; D010455:Peptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C089502:sarafotoxin-c; C057354:sarafotoxins s6; D000242:Cyclic AMP; D019204:GTP-Binding Proteins