Studies on beta-adrenoceptors mediating changes in mechanical events and adenosine 3',5'-monophosphate levels. Guinea-pig trachea.

In quinea-pig tracheal smooth muscle, (?)-isoproterenol and (?)-soterenol increase cyclic AMP levels, the latter being classified as a partial agonist. The ED₅₀ values were 1.74 × 10^?7 M and 2.48 × 10^?7M for isoproteronol and soteronol, respectively. Isoproterenol and soterenol were also examined as competitive antagonists of isoproterenol-induced increase in cyclic AMP levels. The apparent dissociation constants calculated from dose ratios for antogonism were 2.19 × 10^?8 M for isoproterenol and 08.38 × 10^?8 M for soterenol. These values are the same as apparent dissociation constants obtained in previous studies on relaxation produced by these agonsits. Carbachol, the functional antagonist use to estimate agonist dissociation constants for production of relaxation, antagonized isoproterenol- and soterenol-induced increases in cyclic AMP only in the central region of their dose-response curves without blocking effects of small or large doses of either agonist. This antagonism was demonstrated to be calcium-dependent. The results are consistent with the view that β-receptors mediating relaxation and diseases in cyclic AMP levels in guinea-pig trahea are of the same type and that differences in concentrations required to elicit the two responses is a result of the receptor reserve. A larger receptor reserves for β-agonist in tracheal smooth muscle vs. heart is considered to be a major determinant in quantitative responses produced in the two tissues.