Beta-2-Adrenoceptors Mediate Inhibition Of Carbachol-Induced Contraction And Camp Generation In Isolated Smooth-Muscle Cells From Rabbit Gastric Antrum

The regulation of inhibition of carbachol-induced contraction by beta-adrenoceptors of rabbit gastric antrum has been investigated. A functional assay using isolated smooth muscle cells (ISMC) was used to study the effect of beta-adrenergic agonists and antagonists on carbachol-contracted ISMC and cAMP generation. The nonselective beta-adrenergic agonist isoproterenol caused concentration-related inhibition of carbachol-induced contraction associated with a significant increase in cellular cAMP. The EC50 for the effect of isoproterenol on cell inhibition of carbachol-induced contraction was closely related to the EC50 for cAMP formation; the two curves were superimposable, indicating a positive correlation between the biological activity (inhibition of carbachol-induced contraction) and the intracellular event (cAMP formation) caused by the activation of beta-adrenoceptors. The kinetic studies demonstrate that maximum inhibition of carbachol-induced contraction and a parallel elevation of intracellular cAMP content were reached at 30 sec of incubation with isoproterenol. The beta2-selective receptor agonist terbutaline induced inhibition of carbachol-induced contraction of carbachol-contracted ISMC and cAMP generation. However, the relatively beta1-selective receptor agonist norepinephrine had no significant effect Propranolol, a nonselective beta-adrenoceptor antagonist (beta1 and beta2) caused a significant inhibition of the carbachol-induced contraction and rise in cAMP induced by isoproterenol and terbutaline, while the beta1-selective adrenergic receptor antagonist metoprolol, even at higher concentration, was inactive. These data demonstrate that there is a correlation between inhibition of carbachol-induced contraction and cAMP generation upon activation of the beta2-adrenoreceptors in the ISMC of rabbit gastric antrum.