Postjunctional alpha 1-adrenoceptors: preferential innervation of alpha 1-adrenoceptors and the role of neuronal uptake.

Postsynaptic alpha 2-adrenoceptors have been reported to mediate pressor responses in vivo in several species. It has been suggested that it is the presence of these receptors that renders the pressor response to injected noradrenaline resistant to the alpha 1-adrenoceptor antagonist prazosin in these species. We have now investigated this phenomenon in the perfused cat spleen preparation in vitro. We find that the pressor responses to nerve stimulation and phenylephrine are blocked to a greater extent by prazosin than the responses to either noradrenaline or the selective alpha 2-agonist M7. In the presence of cocaine the increases in spleen perfusion pressure induced by noradrenaline, phenylephrine, and nerve stimulation are equally blocked by prazosin. We conclude from these results that the responses of the perfused spleen to exogenous noradrenaline are resistant to prazosin because the access of noradrenaline to alpha 1-adrenoceptors is limited by the neuronal uptake mechanism. The difference in the sensitivity of neuronally released and exogenously administrated noradrenaline to blockade by prazosin may be due to the preferential noradrenergic innervation of alpha 1-adrenoceptors, and the predominant extrasynaptic location of alpha 2-adrenoceptors in vascular smooth muscle.