Endothelin ETA-receptors couple to inositol phosphate formation and inhibition of adenylate cyclase in human right atrium.
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.
Vogelsang
M
M
Biochemical Research Laboratory, Medizinische Klinik and Poliklinik, University of Essen, Germany.
Broede-Sitz
A
A
Schäfer
E
E
Zerkowski
H R
HR
Brodde
O E
OE
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
D000067956:Adenylyl Cyclase Inhibitors; D016232:Endothelins; D007295:Inositol Phosphates; D017466:Receptors, Endothelin; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol