Inhibition by dopamine of 3H-noradrenaline release elicited by nerve stimulation in the isolated cat's nictitating membrane.

Abstract

After loading the isolated nerve muscle preparation of the cat nictitating membrane with 3H-(+/-) -noradrenaline the effects of exogenous dopamine and (-)- noradrenaline were determined on 3H-transmitter overflow elicited by nerve stimulation in the presence of cocaine, 29 muM. Dopamine, 0.20 muM, and (-)- noradrenaline, 0.18 muM, inhibited 3H-noradrenaline release elicited by nerve stimulation at 4 or 10 Hz. Similar results were obtained with apomorphine 0.03 or 0.1 muM. Chlorpromazine, 1 muM, or pimozide, 1 muM, antagonized selectively the reduction in 3H-noradrenaline release obtained with dopamine or apomorphine, without affecting the inhibition obtained with (-)-noradrenaline. Phentolamine, 1 muM, antagonized more effectively the inhibitory effects of (-)-noradrenaline than those of dopamine. Phenoxybenzamine, 0.29 muM, prevented the inhibition of 3H-transmitter overflow obtained with (-)-noradrenaline, dopamine or apomorphine. In the absence of cocaine neither chlorpromazine nor pimozide were able to increase 3H-transmitter overflow during nerve stimulation. Inhibition by dopamine probably located in the outer surface of adrenergic nerve endings. These dopamine receptors differ from the prejunctional alpha-noradrenaline release by nerve stimulation. The prejunctional inhibitory dopamine receptors are not involved in an endogenously mediated regulatory mechanism for noradrenaline release by nerve stimulation under normal conditions. The possibility that these dopamine receptors are involved in the hypotension commonly observed in patients with chronic L-Dopa treatment is discussed.