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.

A dopaminergic receptor modulates catecholamine release from the cat adrenal gland.

“…Later, many other receptors were implicated in the modulation ofnoradrenaline release; the concept of transmitter modulation by such receptors was extended to several neurotransmitters, both peripherally and centrally (Kirpekar, 1975; Stjirne, 1975;Starke, 1977;Westfall, 1977;Langer, 1981). One of these, the dopaminergic receptor, was shown to modulate noradrenaline release from several peripheral sympathetic neuroeffector junctions (Langer, 1973;Long, Heintz, Cannon & Kim, 1975;Enero & Langer, 1975;Steinsland & Hieble, 1978); when activated, these receptors mediate inhibition of electrically evoked noradrenaline release. In addition, at sympathetic ganglia dopamine receptors mediate the slow inhibitory post-synaptic potential, facilitate the slow excitatory post-synaptic potential (Libet, 1970) and cause the activation of adenylate cyclase (Kebabian & Greengard, 1971).…”

Release of 5‐hydroxytryptamine, dopamine and noradrenaline in the rat vas deferens in the presence of compound 48/80, veratridine or K+

“…However, there is now evidence that sympathetic nerve endings as well as smooth muscle possess dopamine receptors (Enero & Langer, 1975;Simon & Van Maanen, 1976;Tayo, 1979;Ohlstein & Berkowitz, 1985). In addition, the release of dopamine together with NA has been detected in several experimental conditions (Soares-da-Silva, 1987; see also review by Bell, 1988).…”

Pharmacological Differentiation of Presynaptic Inhibitory Α‐adrenoceptors and Opiate Receptors in the Cat Nictitating Membrane

“…Attention should be drawn to the fact that the use of high concentrations of phenoxybenzamine is not a selective pharmacological tool for the analysis of the presynaptic effects of several drugs. In this respect, it was found that phenoxybenzamine antagonizes the inhibition of noradrenaline release mediated by presynaptic dopamine receptors in the cat nictitating membrane (Enero & Langer, 1975). Moreover, Walton, Liepmann & Baldessarini (1978) have shown that phenoxybenzamine blocks the dopamine-induced stimulation of adenylate cyclase activity in homogenates of rat striatum.…”