Affinity of Noradrenaline and dopamine for neural alpha-receptors mediating negative feedback control of noradrenaline secretion in human vasoconstrictor nerves

Abstract

Isolated superfused field stimulated biopsy specimens of human peripheral arteries and veins, preincubated with 3H-( - )-NOradrenaline (NA) to label the neural stores of NA, were used to study the potency of dopamine (DA) and of NA as triggers of alpha-adrenoceptor mediated negative feedback control of sympathetic neurotransmitter secretion, evoked by stimulation with trains of 300 shocks at 1 Hz. In this preparation DA was found to be only slightly less potent than NA in depressing both the secretion of 3h-na, and the contractile response, evoked by nerve stimulation. DA depressed the contraction evoked by exogenous NA as well, but to a very much smaller extent. On the other hand, DA was a very weak agonist on the alpha receptors of the smooth muscle; nearly 1000 times higher concentrations of DA were required to mimick contractions evoked by exogenous NA. The results show that the neural alpha-receptor function involved in control of NA secretion differs considerably from the alpha-receptors of e.g. smooth muscle, with respect to sensitivity to DA. It seems possible that the observed depressing effect of DA on NA secretion may be of pharmacological and clinical interest; it may at least in part explain the vasodilating effect of DA infusions in man.