SELECTIVE ACTIVATION BY LY-141865 AND APOMORPHINE OF PRESYNAPTIC DOPAMINE-RECEPTORS IN THE RAT-KIDNEY AND INFLUENCE OF STIMULATION PARAMETERS IN THE ACTION OF DOPAMINE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (1) , 161-167
Abstract
The presence and physiological role of presynaptic dopamine receptors in the isolated-perfused rat kidney was assessed by determining the effects of several agonists and antagonists on the release of [3H]norepinephrine elicited during periarterial nerve stimulation. In the presence of cocaine, dopamine caused a concentration-dependent inhibition of stimulus-induced release of [3H]norepinephrine at 0.5 and 2 Hz. Phentolamine as well as sulpiride caused partial antagonism of the inhibitory action of dopamine at 0.5 Hz (20 s) and a combination of both of these agents was required to completely antagonize the action of dopamine. The inhibition of [3H]norepinephrine release caused by dopamine at 2 Hz (20 s) was completely antagonized by sulpiride alone and phentolamine had no effect on the inhibitory action of dopamine. Dopamine-induced inhibition of norepinephrine release apparently depends on the conditions of stimulation, i.e., during lower frequencies of sympathetic nerve stimulation, inhibition occurs by simultaneous activation of both presynaptic dopamine receptors as well as .alpha. adrenoceptors, whereas only presynaptic dopamine receptors are responsible for the inhibition of neurotransmitter release caused by dopamine at the higher frequency of nerve stimulation. The dopamine receptor agonists apomorphine and LY-141865 caused concentration-dependent inhibition of [3H]norepinephrine release elicited during periarterial nerve stimulation at 0.5 Hz, which was antagonized by sulpiride but not by phentolamine, suggesting that selective stimulation of presynaptic dopamine receptors accounted for inhibitory actions of these compounds. In the presence of cocaine, norepinephrine also inhibited stimulus-induced release of [3H]norepinephrine at 0.5 Hz, which could be antagonized by phentolamine but not sulpiride. Sulpiride by itself did not alter the release of [3H]norepinephrine during periarterial nerve stimulation at either 0.5 or 2 Hz. Presynaptic inhibitory dopamine receptors are evidently present on sympathetic nerves in the rat kidney. Whereas these receptors do not appear to play a physiological role in modulating sympathetic neurotransmitter release, they represent an important pharmacological target site for the action of selective dopamine receptor agonists.