Vascular smooth muscle: availability of calcium through alpha-adrenoceptor stimulation.

In strip preparations from the rabbit main pulmonary artery, it was not possible to differentiate convincingly between alpha 1- and alpha 2-adrenoceptors, when selective agonists such as methoxamine, St 587, B-HT 920, and clonidine, as well as selective antagonists such as prazosin and yohimbine were used for receptor characterization. Measurements of the membrane potential of the vascular smooth-muscle cells with intracellular glass micropipettes showed similar depolarizations in response to the alpha 1-selective methoxamine and the alpha 2-selective B-HT 920. These observations suggest the occurrence of a uniform alpha-adrenoceptor population in the rabbit main pulmonary artery. However, in contrast to alpha 1-agonists, contractile responses to alpha 2-agonists differed considerably in their dependence on external Ca, as revealed in Ca withdrawal experiments, as well as by the use of Ca antagonists. Furthermore, inactivation of the guanine nucleotide-binding inhibitory protein (Ni protein) by pertussis toxin impaired vasoconstriction, in response to alpha 2-agonists, but left that to alpha 1-agonists unaffected. It is suggested that alpha 1- and alpha 2-agonists induce two distinct conformational changes in an otherwise uniform alpha-adrenoceptor of the rabbit main pulmonary artery. By the mediation of Ni protein, alpha 2-agonists appear to allow influx of Ca into the vascular muscle cells through a type of Ca channel that is unlikely to be controlled by voltage.