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.
Pretreatment of guinea pigs with paragyline (100 mg/kg i.p., 18 hr before sacrifice) resulted in 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 on total 3H, [3H]NE or endogenous NE release, suggesting the possibility that more than one 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 4-1284), increased the nerve stimulation-mediated overflow of all the measured indices of neurotransmitter release, in addition to producing 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. These results would tend to eliminate a causal role for a deaminated metabolite of NE in the augmenting effect on release seen with RO 4-1284. Conversely, 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.
D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000494:pharmacology*; D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000032:analysis; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
D011807:Quinolizines; D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; D010293:Pargyline; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine