Central and peripheral alpha-adrenoceptors.

The recent interest in the characterization and functional, role of alpha-adrenoceptors has prompted us to study the following different, although interdigitated, lines of research: (a) The functional role of calcium ions in the process of vasoconstriction, induced by alpha 2-adrenoceptor stimulation. We have shown in various animal species that the vasoconstriction induced by alpha 2-adrenoceptor stimulation with specific agonists is impaired by various organic and inorganic calcium antagonists. This finding suggests that the influx of extracellular calcium is required in order to enable the occurrence of vasoconstriction, mediated by the stimulation of vascular alpha 2-adrenoceptors. (b) The functional role of cardiac presynaptic alpha 2-adrenoceptors in the bradycardiac effect of clonidine and related congeners. In the pentobarbitone-anaesthetized rat, the stimulation of cardiac presynaptic alpha 2-adrenoceptors appears to be a highly relevant mechanism, which in combination with the facilitation of the vagal reflex bradycardia explains the bradycardiac action of clonidine and related drugs. (c) The possible extrasynaptic location of postsynaptic alpha 2- and beta 2-adrenoceptors in vascular smooth muscle. A comparison of the influence of the blocking potency of selective alpha 1- and alpha 2-adrenoceptor antagonists on the vasoconstrictor and tachycardia effects of catecholamines, either released endogenously or injected via an exogenous route, has suggested that the alpha 2- and beta 2-adrenoceptors are probably located at extrasynaptic sites, whereas the alpha 1-adrenoceptors are rather situated within the synapse. (d) The characterization of alpha-adrenoceptors involved in the central hypotensive and sedative activities of clonidine. Experiments with selective alpha-adrenoceptors blocking agents have revealed that the central alpha-adrenoceptors involved in the hypotensive and sedative effects of clonidine are most likely to correspond to the alpha 2-subtype.