EFFECTS OF DOPAMINE AND -METHYL-DOPAMINE ON SMOOTH MUSCLE AND ON THE CARDIAC PACEMAKER

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The action of dopamine and -methyl-dopamine was studied on the nictitating membrane of the spinal cat and on the pacemaker of isolated guinea-pig atria. In both organs, dopamine had direct (reserpine-resistant) and indirect (reserpine-sensitive) effects. The introduction of an -methyl group decreased the potency of the direct and increased the indirect effects. The -methylated derivatives appear to be more potent releasers of norepinephrine than the non-methylated amines, probably because the former are not metabolized by intraneuronal monoaminoxidase. Chronic decentralization of the nictitating membrane increased the sensitivity to both amines equally and moderately. Chronic denervation and cocaine, on the other hand, potentiated dopamine much more than -methyl-dopamine. No evidence was obtained for the view that the conversion of either of the amines to norepinephrine and -methyl-norepinephrine, respectively, contributes to the pharmacologic responses obtained by injections or infusions of the parent amines. On the other hand, evidence was obtained for the view that dopamine not only releases endogenous norepinephrine but also prevents the reuptake of the released transmitter. Consequently, at least three different mechanisms contribute to a pharmacologic response to dopamine: 1) a direct action on the -receptors (nictitating membrane) or -receptors (pacemaker), 2) a release of endogenous norepinephrine, and 3) an impairment of the reuptake of the released norepinephrine. It also appears likely that during a continuous infusion of dopamine into a spinal cat, a gradual increase of the amine at the receptors of the innervated nictitating membrane takes place, presumably because of a gradually increasing saturation of the uptake mechanism for dopamine.

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