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.