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Arch Int Pharmacodyn Ther. 1981 Jan;249(1):26-38.

On the coexistence of beta 1- and beta 2-adrenoceptors in various organs.


In rabbit left atrium and ileum as well as in guinea-pig tracheal chain preparations dose-response curves for isoprenaline, adrenaline, noradrenaline and fenoterol have been determined. In order to assess the coexistence of beta 1- and beta 2-adrenoceptor subtypes in these tissues the antagonism of the relative selective adrenolytic drugs metoprolol (beta 1-) and H35/25 (beta 2-) against these sympathomimetic agents was tested. The determination of the pD2-values for the agonists showed a relative high affinity of fenoterol and adrenaline to tracheal beta-adrenoceptors whilst noradrenaline was most affine to atrial beta-adrenoceptors. In all three organs isoprenaline showed the highest affinity. On rabbit atrium driven by 1 Hz both beta-adrenolytic drugs competitively inhibited the effects of all sympathomimetic agents. The pA2-values characterizing the antagonism between metoprolol and isoprenaline, adrenaline or noradrenaline were comparable. Those determined for the interaction of H35/25 with these agonists also were in the same range but lower than those for metoprolol. Both adrenolytic drugs showed higher pA2-values to fenoterol. Furthermore for classification of beta-adrenoceptor binding sites the method of Paton and Rang (1965) was applied. The dose-ratio of isoprenaline after combination of metoprolol and H35/25 was multiplicative thus confirming the existence of different binding sites in the atrium. On rabbit ileum pA2-values for both antagonists could only be determined when isoprenaline was the agonist. The effect of the endogenous catecholamines, adrenaline and noradrenaline, was only blocked by metoprolol. On the other hand, fenoterol could not be blocked by either antagonist alone, but only by the combination of both adrenolytic drugs indicating a comparable affinity of fenoterol to both binding sites.--The Schild-plot for the antagonism of propranolol versus noradrenaline or fenoterol supports the view of the existence of different types of adrenoceptors stimulated by either agonist. On the guinea-pig tracheal chain both adrenolytic drugs inhibited competitively the effects of the sympathomimetic agonists. The pA2-values for H35/25 where the highest when compared with those of atrium or ileum. Using the combination of metoprolol and H35/25 the resulting dose-ratio for adrenaline was multiplicative demonstrating again the presence of two binding sites. The present results indicate the coexistence of beta 1- and beta 2-adrenoceptor subtypes on the organs investigated. This conclusion has been reached by the use of at least two methods in parallel, namely the determination of the pA2-values for selective antagonists to selective agonists and that for a nonselective antagonist to selective agonists and furthermore, the calculation of the dose-ratio of agonists after the combined administration of two selective antagonists.

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