Isoproterenol changes the relationship between cytosolic Ca2+ and contraction in guinea pig taenia caecum.
To determine the role of beta-adrenoceptors in the regulation of intestinal smooth muscle, the action of isoproterenol (ISO) on cytoplasmic Ca2+ level ([Ca2+]cyt) and mechanical activity in the isolated guinea pig taenia caecum was examined. Spontaneous changes in [Ca2+]cyt and contraction were inhibited by ISO (0.1-1 microM) without changing resting [Ca2+]cyt. ISO more strongly inhibited the histamine-induced contraction than the high K(+)-induced contraction. ISO inhibited muscle tension more strongly than [Ca2+]cyt stimulated by high K+ and thus shifted the [Ca2+]cyt-tension curve to the lower-right. In the muscle stimulated by histamine, on the other hand, ISO inhibited both [Ca2+]cyt and tension. Salbutamol, a beta 2-selective agonist, showed similar effects as ISO on spontaneous, high K(+)- and histamine-stimulated [Ca2+]cyt and tension. Stimulation of beta-adrenoceptors by ISO increased cyclic AMP content without changing cyclic GMP content. These results suggest that activation of beta 2-adrenoceptors by ISO inhibits the contractions by two mechanisms of action: decrease in Ca2+ sensitivity of contractile elements in the muscle stimulated by K(+)-depolarization and decrease in [Ca2+]cyt in the muscle stimulated by histamine. These effects may be mediated by cyclic AMP.
Kwon
S C
SC
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Ozaki
H
H
Hori
M
M
Karaki
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002432:Cecum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D006632:Histamine; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium