The effects of isoproterenol on intracellular calcium concentration.
beta-Adrenergic agonist, isoproterenol (ISO), is a potent relaxant of tracheal smooth muscle and inhibits carbachol-induced contraction. The effect of ISO on intracellular free Ca2+ concentration ([Ca2+]i) was examined in bovine tracheal smooth muscle strips, employing aequorin as Ca2+ indicator. Surprisingly, 10 microM ISO induces a 5-fold increase in [Ca2+]i which then gradually declines but still remains higher than basal after 1 h of stimulation. The ISO-induced increase in [Ca2+]i is dose-dependent, and the ED50 is approximately 50 nM. The ISO-induced increase in [Ca2+]i is inhibited by a beta-receptor blocker, propranolol, not by an alpha-blocker, phentolamine. The ISO-induced rise in [Ca2+]i is dependent on extracellular Ca2+. Forskolin, an adenylate cyclase activator, and vasoactive intestinal peptide, which is known to stimulate adenylate cyclase via a specific receptor in this tissue, have similar effects on [Ca2+]i, suggesting that a rise in cyclic AMP concentration mediates this effect of ISO on [Ca2+]i. Pretreatment of muscle with 10 microM ISO inhibits both the initial Ca2+ transient and the contractile response induced by 0.3 microM carbachol. Conversely, in carbachol-pretreated muscle strips, addition of ISO causes a fall rather than a rise in [Ca2+]i, and an inhibition of contraction. These results indicate that ISO has effects on cellular Ca2+ metabolism at more than a single site in bovine tracheal smooth muscle, that these effects are different in control and carbachol-pretreated muscle, and that the relaxing effect of ISO is not due solely to its effect on Ca2+ metabolism.
Takuwa
Y
Y
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Takuwa
N
N
Rasmussen
H
H
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D010703:Phorbol Esters; D005576:Colforsin; C039067:12-deoxyphorbol 13-isobutyrate; D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D002217:Carbachol; D011433:Propranolol; D007545:Isoproterenol; D002118:Calcium