Abstract
2-Phenylethylamine (PE) is an endogenous brain amine which produces sympathomimetic responses and potentiates cortical neuron responses to noradrenaline (NA). In order to examine further the mechanism of action of PE, extracellular recordings were made of the activity of single neurones in the cerebral cortex in urethane-anesthetized rats. Sympathomimetic responses to PE were blocked by pretreatment with reserpine, reserpine plus α-methyl-p-tyrosine and desipramine. It is concluded that the sympathomimetic responses to PE are indirect. 2-Phenylethylamine potentiated cortical neuron responses to electrical stimulation of the locus coeruleus in a dose-dependent manner. This was seen when PE was given systemically (with as little as 1 μg/kg) and iontophoretically. The effects of PE were not reproduced by its metabolite phenylacetic acid or its putative metabolite phenylethanolamine. Iontophoretic applications of PE (0–6 nA, 2–5 minutes) potentiated cortical neuron responses to iontophoretically applied NA, without affecting the spontaneous firing rate, or the responses to iontophoretically applied GABA or acetylcholine. This effect of PE was not blocked by pretreatment with α-methyl-p-tyrosine or desipramine, and was potentiated by pretreatment with reserpine and reserpine plus α-methyl-p-tyrosine. It is probable that the ability of PE to modulate neuronal responses to NA does not involve the presynaptic NA terminal or endogenous NA and it is likely that PE acts directly to increase the efficacy of NA. These findings are consistent with the hypothesis that the physiological role of PE is to modulate catecholaminergic transmission within the central nervous system.
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References
Bertler, A. 1961. Effect of reserpine on the storage of catecholamines in brain and other tissues. Acta Physiol. Scand. 51:75–83.
Boulton, A. A. 1976. Cerebral aryl alkyl aminergic mechanisms. Pages 22–39in: Usdin, E., Sandler, M. (eds.) Trace Amines and the Brain, New York, Marcel Dekker.
Boulton, A. A. 1980. The trace amines: Neurohumours (cytosolic, pre- and/or postsynaptic, sinaptic, secondary, indirect). Behav. Brain Sci. 7:418.
Dourish, C. T. 1981. Behavioural effects of acute and chronic β-phenylethylamine administration in the rat: evidence for the involvement of 5-hydroxytryptamine. Neuropharmacol. 20:1067–1072.
Durden, D. A., Philips, S. R. and Boulton, A. A. 1973. Identification and distribution of β-phenylethylamine in the rat. Can. J. Biochem. 51:995–1002.
Dyck, L. E. 1983. Release of monoamines from striatal slices by phenelzine and β-phenylethylamine. Prog. Neuropsychopharmacol. Biol. Psychiat. 7:797–800.
Dyck, L. E. 1988. Release of some endogenous trace amines from rat striatal slices in the presence and absence of a monoamine oxidase inhibitor. In: Boulton, A. A., Juorio, A. V., Downer, R. G. H. eds. Trace Amines: Comparative and Clinical Neurobiology. Clifton NJ, Humana Press, 1988:223–237.
Dyck, L. E., Yang, C. R., Boulton, A. A. 1983. The biosynthesis ofptyramine,mtyramine, and β-phenylethylamine by rat striatal slices. J. Neurosci. Res. 10:211–220.
Fuxe, K., Grobecker, H.; Jonsson, J. 1967. The effect of β-phenylethylamine on central and peripheral monoamine containing neurones. Eur. J. Pharmacol. 2:202–207.
Harris, J., Trivedi, S., Ramakrishna, B. L. 1988. A contribution to the neuromodulatory/neurotransmitter role of trace amines. Pages 213–221in: Boulton, A. A.; Juorio, A. V.; Downer, R. G. H. eds.. Trace Amines: Comparative and Clinical Neurobiology, Clifton NJ, Humana Press.
Hauger, R. L., Skolnick, P., Paul, S. M. 1982. Specific (3H)-β-phenylethylamine binding sites in the rat brain. Eur. J. Pharmacol. 83:147–148.
Henwood, R. A., Boulton, A. A., Phillis, J. W. 1979. Iontophoretic studies of some trace amines in the mammalian CNS. Brain Res. 164:347–351.
Holzbauer, M., Vogt, M. 1956. Depression by reserpine of the noradrenaline concentration in the hypothalamus of the cat. J. Neurochem. 1:8–11.
Horn, A. D., Snyder, S. H. 1973. Steric requirements for catecholamine uptake by rat brain synaptosomes: studies with rigid analogues of amphetamine. J. Pharmacol. Exp. Ther. 180:523–530.
Jackson, D. M. 1978. β-Phenylethylamine studies on the mechanisms of its stimulant effects. Pages 289–313in: Mosnaim, A. D., Wolf, M. E. (eds.) Noncatecholic Phenylethylamines—Part 1 Phenylethylamine: Biological Mechanisms and Clinical Aspects. New York, Marcel Dekker.
Jackson, D. M. 1988. 2-Phenylethylamine, dopamine, and behaviour. Pages 429–432in: Sandler, M., Dahlström, A., Belmaker, R. H. (eds.) Progress in Catecholamine Research. Part B: Central Aspects, New York, Alan R Liss Inc.
Jones, R. S. G., Boulton, A. A. 1980. Interactions betweenptyramine,mtyramine or β-phenylethylamine and dopamine on single neurones in the cortex and caudate nucleus of the rat. Can. J. Physiol. Pharmacol. 58:222–227.
Juorio, A. V. 1988. Brain-β-phenylethylamine: Localization, Pathways, and Interrelation with Catecholamines. Pages 433–437in: Sandler, M., Dahlström, A., Belmaker, R. H. (eds.) Progress in Catecholamine Research. Part B: Central Aspects, New York, Alan R. Liss Inc..
Juorio, A. V., Greenshaw, A. J., Wishart, T. B. 1988. Reciprocal changes in striatal dopamine and β-phenylethylamine induced by reserpine in the presence of monoamine oxidase inhibitors. Naunyn-Schmiedeberg's Arch. Pharmacol. 338:644–648.
Karoum, F., Speciale S. G. J., Chuang, L. W., Wyatt, R. J. 1982. Selective effects of phenylethylamine on central catecholamines: a comparative study with amphetamine. J. Pharmacol. Exp. Ther. 223:432–439.
Li, X-M., Juorio, A. V., Paterson, I. A. and Boulton, A. A. 1992. Absence of 2-phenylethylamine binding after monoamine oxidase inhibition in rat brain. Eur. J. Pharmacol. 210:189–193.
Lundberg, P-A., Oreland, L., Engberg, G. 1985. Inhibition of locus coeruleus neuronal activity by β-pheylethylamine. Life Sci. 36:1889–1896.
Paterson, I. A. 1988. The potentiation of cortical neurone responses to noradrenaline by β-phenylethylamine effects of lesions of the locus coeruleus. Neurosci. Lett. 87:139–144.
Paterson, I. A., Boulton, A. A. 1988. β-Phenylethylamine enhances single cortical neurone responses to noradrenaline in the rat. Brain Res. Bull. 20:173–177.
Paterson, I. A., Hertz, I. 1989. Sodium-independent transport of noradrenaline in mouse and rat astrocytes in primary culture. J. Neurosci. Res. 23:71–77.
Paterson, I. A., Juorio, A. V. and Boulton, A. A. 1990. 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system? J. Neurochem. 55:1827–1837.
Paterson, I. A., Juorio, A. V., Berry, M. D. and Zhu, M. Y. 1991. Inhibition of monoamine oxidase-B by (−)-deprenyl potentiates neuronal responses to dopamine agonists but does not inhibit dopamine catabolism in the rat striatum. J. Pharmacol. Exp. Ther. 258:1019–1026.
Paxinos, G., Watson, C. 1982. The Rat Brain in Stereotaxic Coordinates. New York, Academic Press.
Philips, S. R., Rozdilsky, B., Boulton, A. A. 1978. Evidence for the presence ofmtyramine,ptyramine, tryptamine and phenyethylamine in the rat brain and several areas of the human brain. Biol. Psychiat. 13:51–57.
Raiteri, M., Del Carmine, R., Bertollini, A., Levi, G. 1977. Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine. Eur. J. Pharmacol. 41:133–143.
Reynolds, G. P., Sandler, M., Hardy, J., Bradford, H. 1980. The determination and distribution of 2-phenylethylamine in sheep brain. J. Neurochem. 34:1123–1125.
Sabelli, H. C., Vazquez, A. J., Flavin, D. 1975. Behavioural and electrophysiological effects of phenylethanolamine and 2-phenylethylamine. Psychopharmacol. 42:117–125.
Shannon, H. E., DeGregorio, C. M. 1982. Self-administration of the endogenous trace amines β-phenylethylamine, N-methylphenylethylamine and phenylethanolamine in dogs. J. Pharmacol. Exp. Ther. 222:52–60.
Sloviter, R. S., Conner, J. D., Drust, E. G. 1980. Serotonergic properties of β-phenylethylamine in rats. Neuropharmacol. 19:1071–1074.
Wu, P. H., Boulton, A. A. 1975. Metabolism, distribution and disappearance of injected β-phenylethylamine in the rat. Can. J. Biochem. 53:42–50.
Yu, P. H. 1986. Monoamine Oxidase. Pages 235–272in: Boulton, A. A., Baker, G. B., Yu, P. H. (eds.) Neuromethods, Volume 5, Neurotransmitter, Enzymes. Clifton, NJ, Humana Press.
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Paterson, I.A. The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline. Neurochem Res 18, 1329–1336 (1993). https://doi.org/10.1007/BF00975055
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DOI: https://doi.org/10.1007/BF00975055