title: Endothelin ETA-receptors couple to inositol phosphate formation and inhibition of adenylate cyclase in human right atrium.
abstract: To study signal transduction pathways of endothelin (ET) in human heart, we assessed, in isolated human right atria, the effects of ET-1 and ET-3 on inositol phosphate (IP) formation and on the adenylate cyclase/cyclic AMP system. In right atrial slices, ET-1 (10(-10)-10(-6)M) concentration-dependently increased [3H]IP accumulation and decreased 10-microM isoprenaline-induced or 1-microM forskolin-induced increases in cyclic AMP content. ET-3 was approximately 100 times less potent. The cyclic AMP-decreasing effect of ET-1 (10(-11)-10(-6)M) could also be demonstrated directly in adenylate cyclase assays in right atrial membranes; again, ET-3 was approximately 100 times less potent. We conclude that in human right atrium, ETA receptors couple to two different signal-transduction pathways: IP formation and inhibition of adenylate cyclase.
authors.affiliation: Biochemical Research Laboratory, Medizinische Klinik and Poliklinik, University of Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Vogelsang
authors.forename: A
authors.initials: A
authors.lastname: Broede-Sitz
authors.forename: E
authors.initials: E
authors.lastname: Schäfer
authors.forename: H R
authors.initials: HR
authors.lastname: Zerkowski
authors.forename: O E
authors.initials: OE
authors.lastname: Brodde
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000328:Adult; D000368:Aged; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006325:Heart Atria / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D016232:Endothelins; D007295:Inositol Phosphates; D017466:Receptors, Endothelin; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol