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[Effect of pH changes on the binding of agonists and antagonists to the adrenergic beta receptor].

The effect of pH on [3H]-DHA specific binding and its displacement by various nonlabeled ligands from beta-adrenoreceptors was examined in sarcolemmal membranes from canine hearts. At low pH (6.69) the affinity of beta-adrenoreceptors for agonists is lower than at pH 7.65, causing a 1.50-fold increase in the inhibition constant (KI) of both (-) noradrenaline and (-) isoprenaline. The change in the affinity was attenuated by adding 300 microM GTP to the reaction medium. Low pH neither affected the affinity of antagonists ((-) dihydroalprenolol, (+/- ) alprenolol, ( +/- ) propranolol) for adrenoreceptors nor the number of binding sites determined by [3H]-DHA binding assays. The effect of pH suggests that H+ induces the formation of a low affinity state of beta-adrenoreceptors for agonists. This H+-dependent mechanism may be capable of regulating the process by which agonists stimulate adenyl cyclase.