Summary
Rats were treated once (acute) or once daily for 21 days (chronic) with clorgyline (2 mg/kg) or nialamide (50 mg/kg). (−)Deprenyl (1 mg/kg) was given for 21 days. One day after the last injection, vas deferens and anococcygeus muscles were removed and noradrenaline stores labelled with 3H-noradrenaline. Efflux of total tritium following electrical field stimulation was decreased by both acute and chronic treatment with clorgyline and nialamide, as well as by chronic treatment with deprenyl. Total tritium release from anococcygeus muscle was reduced by both acute and chronic treatment with clorgyline. Fractionation of the effluent showed that release of both free noradrenaline and metabolites was decreased by MAO inhibitor treatment in vivo, but this effect was not reproduced by in vitro incubation of the vas deferens with clorgyline (1 μM). By contrast to the effect of electrical field stimulation, release of 3Hnoradrenaline induced by veratrine was increased by chronic treatment with both clorgyline and nialamide. Release of total tritium by depolarising concentrations of KCl was also increased by chronic clorgyline treatment. These results could be explained by a proportionally greater release of tritium from a cytoplasmic compartment following veratrine and KCl than electrical stimulation, since MAO inhibition increases cytoplasmic noradrenaline levels. Alternatively, release by electrical stimulation may be affected to a greater extent by presynaptic α2-adrenoceptors, and presynaptic receptors may be stimulated by increased synaptic levels of free noradrenaline following MAO inhibition.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bayorh MA, Zukowska-Grojec Z, Kopin IJ (1983) Effect of desipramine and cocaine on plasma norepinephrine and pressor responses to adrenergic stimulation in pithed rats. J Clin Pharmacol 23:24–31
Bonisch H, Graefe KH, Keller B (1983) Tetrodotoxin-sensitive and-resistant effects of veratridine on the noradrenergic neurons of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 324:264–270
Caramona MM, Araujo D, Brandao F (1985) Influence of MAO A and MAO B on the inactivation of noradrenaline in the saphenous vein of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 328:401–406
Cohen RM, Campbell IC, Cohen MR, Torda T, Pickar D, Siever LJ, Murphy DL (1980) Presynaptic noradrenergic regulation during depression and anti-depressant drug treatment. J Psychiat Res 3:93–105
Cohen RM, Campbell IC, Dauphin M, Tallman JF, Murphy DL (1982a) Changes in a and β receptor densities in rat brain as a result of treatment with monoamine oxidase inhibiting anti-depressants. Neuropharmacol 21:293–298
Cohen RM, Epstein RP, Daly JW, Murphy DL (1982b) Chronic effects of a monoamine oxidase-inhibiting antidepressant: decreases in functional α-adrenergic autoreceptors precede the decrease in norepinephrine-stimulated cyclic adenosine 3′:5′ monophosphate systems in rat brain. J Neurosci 2:1588–1595
Davey MJ, Farmer JB, Reinert H (1963) The effects of nialamide on adrenergic functions. Br J Pharmacol 20:121–134
Dubocovich ML, Langer SZ (1974) Negative feedback regulation of noradrenaline release by nerve stimulation in the perfused cat's spleen: differences in potency of phenoxybenzamine in blocking the pre- and post-synaptic adrenergic receptors. J Physiol 237:505–519
Farnebo L (1971) Effect of reserpine on release of [3H] noradrenaline, [3H] dopamine and [3H] metaraminol from field stimulated rat iris. Biochem Pharmacol 20:2715–2726
Finberg JPM, Kopin IJ (1986) Chronic clorgyline treatment enhances release of norepinephrine following sympathetic stimulation in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 332:236–242
Finberg JPM, Tal A (1985) Reduced peripheral presynaptic adrenoceptor sensitivity following chronic antidepressant treatment in rats. Br J Pharmacol 84:609–617
Finberg JPM, Tenne M (1982) Relationship between tyramine potentiation and selective inhibition of monoamine oxidase types A and B in the rat vas deferens. Br J Pharmacol 77: 13–21
Gessa GL, Cuenca E, Costa E (1963) On the mechanism of hypotensive effects of MAO inhibitors. Ann NY Acad Sci 107:935–941
Graefe KH, Stefano FJE, Langer SZ (1973) Preferential metabolism of −3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160
Harper B, Hughes IE (1979) Presynaptic α-adrenoceptor blocking properties among tri and tetra cyclic antidepressant drugs. Br J Pharmacol 67: 511–517
Hovevey-Sinn D (1986) Effect of acute and chronic treatment with antidepressants on presynaptic alpha2 adrenoceptors and [3H]-noradrenaline release from sympathetic neurons. D. Sc. thesis, Technion, Israel
Hume WR, Bevan JA (1984) The structure of the peripheral adrenergic synapse and its functional implications. In: Ziegler MG, Lake CR (eds) Norepinephrine. Williams and Wilkins, Baltimore, pp 47–54
Kalsner S (1985) Is there feedback regulation of neurotransmitter release by autoreceptors? Biochem Pharmacol 34:4085–4097
Langer SZ (1970) The metabolism of [3H] noradrenaline released by electrical stimulation from the isolated nictitating membrane of the cat and from the vas deferens of the rat. J Physiol 208:515–546
Langer SZ (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Lerner P, Major LF, Murphy DL, Lipper S, Lake CR, Lovenberg W (1979) Dopamine beta hydroxylase and norepinephrinein human cerebrospinal fluid: effects of monoamine oxidase inhibitors. Neuropharmacol 18:423–426
Lotti VJ, Chang RSL, Kling P (1981) Pre- and post-synaptic adrenergic activation by norepinephrine reuptake inhibitors in the field-stimulated rat vas deferens. Life Sci 29:633–639
McGrath JC (1977) Adrenergic motor responses to single pulse stimulation in the rat vas deferens. J Physiol 270:52P-53P
Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders. Ann NY Acad Sci 107:1057–1067
Schoffelmeer ANM, Mulder AH (1983) [3H] Noradrenaline release from brain slices induced by an increase in the intracellular sodium concentration: role of intracellular calcium stores. J Neurochem 40:615–621
Sellinger-Barnette MM, Mendels J, Frazer A (1980) The effect of psychoactive drugs on beta-adrenergic receptor sites in rat brain. Neuropharmacol 19:447–454
Stefano FJE, Trendelenburg U (1984) Saturation of monoamine oxidase by intraneuronal noradrenaline accumulation. Naunyn-Schmiedeberg's Arch Pharmacol 328:135–141
Stute N, Trendelenburg U (1984) The outward transport of axoplasmic noradrenaline induced by a rise in the sodium concentration in the adrenergic nerve endings of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 327:124–132
Thoa NB, Wooten GF, Axelrod J, Kopin IJ (1975) On the mechanism of release of norepinephrine from sympathetic nerves induced by depolarizing agents and sympathomimetic drugs. Mol Pharmacol 11:10–18
Trendelenburg U, Draskoczy PR, Graefe KH (1972) The influence of intraneuronal monoamine oxidase on neuronal net uptake of noradrenaline and on sensitivity to noradrenaline. In: Costa E, Sandler M (eds) Monoamine oxidases-new vistas. Raven, New York, pp 371–377
Urwyler S, Von Wartburg J-P (1981) Uptake and metabolism of catecholamines in rat brain synaptosomes: studies on the contribution of monoamine oxidase. Biochem Pharmacol 30:2777–2785
Verbeuren TJ, Vanhoutte PM (1982) Deamination of released 3H-noradrenaline in the canine saphenous vein. Naunyn-Schmiedeberg's Arch Pharmacol 318:146–147
Author information
Authors and Affiliations
Additional information
Send offprint requests to J. P. M. Finberg at the above address
Rights and permissions
About this article
Cite this article
Hovevey-Sion, D., Finberg, J. Chronic inhibition of monoamine oxidase reduces noradrenaline release in rat vas deferens and anococcygeus muscle. Naunyn-Schmiedeberg's Arch Pharmacol 336, 70–76 (1987). https://doi.org/10.1007/BF00177753
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00177753