Species differences in the effects of endothelin-1 on myo-inositol trisphosphate accumulation, cyclic AMP formation and contraction of isolated iris sphincter of rabbit and other species.
The authors investigated the effects of endothelin-1 (ET1) on inositol trisphosphate (IP3) production, 1, 2-diacylglycerol (DAG) formation, measured as phosphatidic acid (PA), cAMP formation, and contraction in iris sphincter of different mammalian species. They found that ET1 is a potent agonist for IP3 production, DAG formation, and contraction in rabbit, dog, cat, and pig iris sphincters, and for cAMP formation in all species that were investigated--rabbit, dog, cat, pig, bovine, monkey, and human sphincters. In the bovine model, ET1 induced cAMP formation in a dose-dependent manner, with an EC50 of 28 nM. This is the first report that showed an effect of the peptide on the adenylate cyclase system. In rabbit sphincter, ET1 induced a significant increase in IP3 production by 30 sec and reached a 6-fold level more than control within 1 and 5 min. ET1-stimulated IP3 production is dose dependent with an EC50 of 45 nM, this value is about 100- and 56-fold lower than those we reported for substance P and carbachol, respectively. ET1 also increased 32P labeling of PA more than 6-fold; and in rabbit sphincter, ET1 is a more potent agonist in contracting the sphincter than in contracting the dilator (the EC50 values for sphincter and dilator were 46 and 120 nM, respectively). L-type Ca2+ channels are not involved in IP3- and contraction responses because several blockers of these channels did not affect the ET1-induced responses, implying that in the iris sphincter, ET1 elicits the physiologic response through the G protein activation of phospholipase C and/or adenylate cyclase and not through the activation of voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdel-Latif
A A
AA
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Zhang
Y W
YW
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007498:Iris / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D010712:Phosphatidic Acids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011680:Pupil / Q000187:drug effects*; D013045:Species Specificity
C011439:1,2-diacylglycerol; D002121:Calcium Channel Blockers; D004075:Diglycerides; D016232:Endothelins; D010712:Phosphatidic Acids; D010743:Phospholipids; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP