THE EFFECT OF PARGYLINE PRETREATMENT ON THE ENHANCEMENT OF THE EXOCYTOTIC RELEASE OF NOREPINEPHRINE DURING NERVE-STIMULATION WHICH IS INDUCED BY A BENZOQUINOLIZINE COMPOUND WITH RESERPINE-LIKE PROPERTIES

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Abstract
Pretreatment of guinea pigs with paragyline (100 mg/kg i.p., 18 h before sacrifice) caused a significant depression in the overflow of endogenous norepinephrine (NE), total 3H, [3H] -NE and dopamine .beta.-hydroxylase associated with stimulation of the sympathetic nerves to the isolated heart. The depression was pronounced at 5 Hz. At 10 Hz, pargyline pretreatment was without effect. The effect on dopamine .beta.-hydroxylase output was not as great as that of total 3H, [3H]NE or endogenous NE release; possibly more than 1 mechanism is responsible for the depressant effect of monoamine oxidase (MAO) inhibition on sympathetic neurotransmission. A benzoquinolizine compound with reserpine-like properties, 2-hydroxy-2-ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11b-H-benzo[.alpha.]quinolizine (Ro 41284), increased the nerve stimulation-mediated overflow of all measured indices of neurotransmitter release and produced a significant increase in the spontaneous overflow of 3H from hearts of untreated guinea pigs. The augmentation of nerve-stimulated NE release by RO 4-1284 was even greater in hearts from pargyline pretreated guinea pigs. Apparently, a deaminated metabolite of NE does not augment the effect on release seen with RO 4-1284. The inhibition of neurotransmitter release associated with MAO inhibition is not mediated by the blockade in the formation of deaminated catecholamine metabolites. Enhancement in the negative feedback mechanism on release and the accumulation of false transmitter probably account for the local effects of MAO inhibitors on neurally mediated norepinephrine release.