Neuronal dopamine receptors of the rabbit ear artery: pharmacological characterization of the receptor.

Abstract

Dopamine and apomorphine were examined in the rabbit isolated perfused ear artery for both direct effects on vascular smooth muscle and effects on the response to field stimulation of sympathetic nerve terminals. The neuroinhibitory effect of both dopamine (EC50 = 37 nM) and apomorphine (EC50 = 44 nM) occurred at concentrations which did not produce vasoconstriction. The neuroinhibitory effect of dopamine was shown to be due to inhibition of noradrenaline release by measurement of 3H-overflow from prelabelled tissues. At relatively high concentrations dopamine produced vasoconstriction. In a superfused segment of ear artery, dopamine was found to be a full agonist at the alpha 1-adrenoreceptor, with an EC50 (15 microM) about 75 fold higher than the EC50 for noradrenaline. At concentrations up to 3 microM, apomorphine had no vasoconstrictor activity in the perfused ear artery. Representative examples of several classes of dopamine antagonists, including the phenothiazines, butyrophenones, diphenylbutylpiperidines and benzamides produced competitive antagonism of dopamine or apomorphine-induced inhibition, with nearly identical Kb values against these two agonists. The pharmacological characteristics of the neuronal dopamine receptor on the rabbit ear artery would indicate this receptor to be typical of the D2 subclass, and this tissue to be a useful model for quantitative studies on dopamine receptor agonists and antagonists.