Skip to main content
SpringerLink
Log in

Down-regulation ofβ-adrenergic and dopaminergic receptors induced by 2-phenylethylamine

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

  1. 1.

    The effects of chronic administration (28 days s.c. via Alzet osmotic minipumps) of 2-phenylethylamine·HC1 (10 mg kg−1 per day) and/or ( − )-deprenyl⋅HC1 (1 mg kg−1 per day) on dopamine and noradrenaline receptor subtypes have been measured in rat brain.3H-CGP 12177 was used to labelβ-adrenoceptors;3H-spiperone and3H-SCH 23390 were used to label D2-like and D1-like receptors.

  2. 2.

    Total corticalβ-adrenoceptor density was reduced by ( − )-deprenyl but not 2-phenylethylamine alone. Combined administration of 2-phenylethylamine and ( − )-deprenyl resulted in a significantly larger decrease than ( − )-deprenyl alone. Subtype density analysis by competition experiments with ICI 89406 revealed that the ( − )-deprenyl effect in cortex was due to a decrease inβ 1-adrenoceptor density. The combination of 2-phenylethylamine and ( − )-deprenyl resulted in a significant decrease in both corticalβ 1- and corticalβ 2-adrenoceptors. Cerebellarβ-adrenoceptor density was not altered by the present drug treatments. TheK d values for totalβ-adrenoceptor densities andK i values forβ-adrenoceptor subtype densities were not altered by drug treatment in either cortex or cerebellum.

  3. 3.

    Administration of 2-phenylethylamine and of ( − )-deprenyl resulted in a decrease in the density of D1-like3H-SCH 23390 but not D2-like3H-spiperone binding to dopamine receptors in the striatum. The effects of combined 2-phenylethylamine and ( − )-deprenyl treatment on3H-SCH 23390 binding were additive. These drug treatments did not alterK d values for these binding sites.

  4. 4.

    The down-regulation of catecholamine receptors following chronically increased availability of 2-phenylethylamine may be due to the catecholamine releasing or uptake blocking effects of this amine. These effects may also be attributable to a direct neuromodulatory action of 2-phenylethylamine on catecholamine receptors.

  5. 5.

    The parallels between effects of increased 2-phenylethylamine availability and effects of administration of MAO inhibitor antidepressants on catecholamine receptor systems indicate that this substrate for MAO may mediate some of the effects of MAO inhibitor antidepressants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baker, G. B., and Greenshaw, A. J. (1989). Effects of long-term administration of antidepressant and neuroleptics on receptors in the central nervous system.Cell. Mol. Neurobiol. 91–44.

    Google Scholar 

  • Baker, G. B., LeGatt, D. F., and Coutts, R. T. (1982). Effects of acute and chronic administration of phenelzine onβ-phenylethylamine levels in rat brain.Proc. West. Pharmacol. Soc. 25417–420.

    Google Scholar 

  • Baker, G. B., Coutts, R. T., Yeung, J. M., Hampson, D. R., McIntosh, G. J. A., and McIntosh, M. G. (1985). Chronic administration of monoamine oxidase inhibitors: Basic and clinical investigations. InNeuropsychopharmacology of the Trace Amines: Experimental and Clinical Aspects; (A. A. Boulton, P. R. Bieck, L. Maitre, and P. Riederer, Eds.); Humana Press, Clifton, N.J., pp. 317–328.

    Google Scholar 

  • Baker, G. B., Greenshaw, A. J., and Coutts, R. T. (1988). Chronic administration of monoamine oxidase inhibitors: Implications for interactions between trace amines and catecholamines. InProgress in Catecholamine Research, Part A: Basic Aspects and Peripheral Mechanisms. Neurology and Neurobiology: (A. Dahlstrom, R. H. Belmaker, and M. Sandler, Eds.), Alan R. Liss, New York, pp. 569–572.

    Google Scholar 

  • Baker, G. B., Bornstein, R. A., Rouget, A. C. Ashton, S. E., van Muyden, J. C., and Coutts, R. T. (1991). Phenylethylaminergic mechanism in attention deficit idsorder.Biol. Psychiat. 2915–22.

    Google Scholar 

  • Beer, M., Hacker, S., Poat, J., and Stahl, S. M. (1987). Independent regulation ofβ 1- andβ 2-adrenoceptors.Br. J. Pharmacol. 92827–834.

    Google Scholar 

  • Bornstein, R. A., Baker, G. B., Carroll, A., King, G., and Ashton, S. (1990). Phenylethylamine metabolism in Tourette's syndrome.J. Neuropsychiat. Clin. Neurosci. 2408–412.

    Google Scholar 

  • Boulton, A. A., and Milward, L. (1971). Separation, determination and quantitative analysis of urinary phenylethylamine.J. Chromatogr. 57187–196.

    Google Scholar 

  • Dooley, D. J., and Bittiger, H. (1987). Quantitative assessment of centralβ 1- andβ 2-adrenoceptor regulation using CGP 20712A.J. Pharmacol. Methods 18131–136.

    Google Scholar 

  • Durden, D. A., and Philips, S. R. (1980). Kinetic measurements of the turnover rates of phenylethylamine and tryptamine in vivo in the rat brain.J. Neurochem. 511725–1732.

    Google Scholar 

  • Dyck, L. E. (1983). Release of monoamines from striatal slices by phenelzine andβ-phenylethylamine.Prog. Neuro-Psychopharmacol. Biol. Psychiat. 7797–800.

    Google Scholar 

  • Dyck, L. E., Durden, D. A., and Boulton, A. A. (1985). Formation ofβ-phenylethylamine from the antidepressant,β-phenylethylhydrazine.Biochem. Pharmacol. 341925–1929.

    Google Scholar 

  • Gottberg, E., Diop, L., Bernard, M., and Reader, T. A. (1989). Effects of sodium, lithium and magnesium on in vitro binding of [3H]-SCH 23390 in rat neostriatum and cerebral cortex.Neurochem. Res. 14419–426.

    Google Scholar 

  • Greenshaw, A. J. (1986). Osmotic minipumps: A convenient program for weight adjusted filling concentrations.Brain Res. 1757–761.

    Google Scholar 

  • Heal, D. J., Butler, S. A., Hurst, E. M., and Buckett, W. R. (1989). Antidepressant treatments, including sibutramine hydrochloride and electroconvulsive shock, decreaseβ 1- but notβ 2-adrenoceptors in rat cortex.J. Neurochem. 531019–1025.

    Google Scholar 

  • Horn, A. S., and Snyder, S. H. (1973). Steric requirements for catecholamine uptake by rat brain synaptosomes: Studies with rigid analogues of amphetamine.J. Pharmacol. Exp. Ther. 180523–530.

    Google Scholar 

  • Klimek, V., and Maj, J. (1990). The effect of antidepressant drugs given repeatedly on the binding of [3H]-SCH 23390 and [3H]-spiperone to dopaminergic receptors. InDopamine and Mental Depression (G. L. Gessa and G. Serra, Eds.), Pergamon Press, New York, pp. 159–166.

    Google Scholar 

  • Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurements with the folin phenol reagent.J. Biol. Chem. 193265–275.

    Google Scholar 

  • McKim, H. R., Calverley, D. G., Philips, S. R., Baker, G. B., and Dewhurst, W. G. (1980). The effects of tranylcypromine on the levels of some cerebral amines in rat diencephalon. InRecent Advances in Canadian Neuropsychopharmacology, (P. Grof and B. Saxena, Eds.), S. Karger, Basel, pp. 7–13.

    Google Scholar 

  • McManus, D. J., Mousseau, D. D., Paetsch, P. R., Wishart, T. B., and Greenshaw, A. J. (1991).β-Adrenoceptors and antidepressants: Possible 2-phenylethylamine mediation of chronic phenelzine effects.Biol. Psychiat. 301122–1130.

    Google Scholar 

  • McPherson, G. A. (1985).Kinetic, EDBA, Ligand, Lowry: A collection of Radioligand Binding Analysis Programs, Elsevier-BIOSOFT, U.K.

    Google Scholar 

  • Minneman, K. P., Dibner, M. D., Wolfe, B. B., and Molinoff, P. (1979a).β1- andβ2-adrenergic receptors in rat cerebral cortex are independently regulated.Science 204866–868.

    Google Scholar 

  • Minneman, K. P., Hegstrand, L. R., and Molinoff, P. B. (1979b). Simultaneous determination ofβ 1-andβ 2-adrenergic receptors in tissues containing both receptor subtypes.Mol. Pharmacol. 1634–46.

    Google Scholar 

  • Munson, P. J., and Robard, D. (1980). LIGAND: A versatile computerized approach to characterization of ligand binding systems.Anal. Biochem. 107220–239.

    Google Scholar 

  • Paetsch, P. R., and Greenshaw, A. J. (1992). Effects of chronic antidepressant treatment on dopamine-related3H-SCH 23390 and3H-spiperone binding in the rat striatum.Cell Mol. Neurobiol. 12597–606.

    Google Scholar 

  • Paetsch, P. R., Baker, G. B., and Greenshaw, A. J. (1993). 2-Phenylethylamine induces functional down-regulation ofβ-adrenoceptors in rats.J. Pharm. Sci. 82 (in press).

  • 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. 551827–1837.

    Google Scholar 

  • Philips, S. R. (1986). In vivo release of endogenous dopamine from rat caudate nucleus byβ-phenylethylamine andα, α-dideutero-β-phenylethylamine.Life Sci. 392395–2400.

    Google Scholar 

  • Philips, S. R., and Boulton, A. A. (1979). The effects of monoamine oxidase inhibitors on some arylalkylamines in rat striatum.J. Neurochem. 33159–167.

    Google Scholar 

  • Philips, S. R., and Robson, A. M. (1983). In vivo release of endogenous dopamine from the rat caudate nucleus by phenylethylamine.Neuropharmacology 221297–1301.

    Google Scholar 

  • Philips, S. R., Baker, G. B., and McKim, H. R. (1980). Effects of tranylcypromine on the concentration of some trace amines in the diencephalon and hippocampus of the rat.Experientia 36241–242.

    Google Scholar 

  • Potkin, S. G., Karoum, F., Chuang, L.-W., Cannon-Spoor, H. E., Phillips, I., and Wyatt, R. J. (1979). Phenylethylamine in chronic paranoid schizophrenia.Science 206470–471.

    Google Scholar 

  • Przegalinski, E., Baran, L., and Siwanowicz, J. (1983). The effect of chronic treatment with antidepressant drugs on salbutamol-induced hypoactivity in rats.Psychopharmacology 80355–359.

    Google Scholar 

  • Przegalinski, E., Baran, L., Siwanowicz, J., and Bigajska, K. (1984). Repeated treatment with antidepressant drugs prevents salbutamol-induced hypoactivity in rats.Pharmacol. Biochem. Behav. 21695–698.

    Google Scholar 

  • Raiteri, M., Del Carmine, R., Bertollini, A., and Levi, G. (1977). Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine.Eur. J. Pharmacol. 41133–143.

    Google Scholar 

  • Riva, M. A., and Creese, I. (1989a). Comparison of two putatively selective radioligands for labeling central nervous systemβ-adrenergic receptors: Inadequacy of [3H]-dihydroalprenolol.Mol. Pharmacol. 36201–210.

    Google Scholar 

  • Riva, M. A., and Creese, I. (1989b). Reevaluation of the regulation ofβ-adrenergic receptor binding by desipramine treatment.Mol. Pharmacol. 36211–218.

    Google Scholar 

  • Rossetti, Z. L., Silvia, C. P., Krajnc, D., Neff, N. H., and Hadjiconstantinou, M. (1990). Aromatic L-amino acid decarboxylase is modulated by D1 dopamine receptors in the rat retina.J. Neurochem. 54787–791.

    Google Scholar 

  • Saavedra, J. M. (1974). Enzymatic isotopic assay for the presence ofβ-phenylethylamine in brain.J. Neurochem. 22211–216.

    Google Scholar 

  • Sabelli, H. C., and Mosnaim, A. D. (1974). Phenylethylamine hypothesis of affective disorder.Am. J. Psychiat. 131695–699.

    Google Scholar 

  • Sabelli, H. C., Fawcett, J., Gusovsky, F., Javaid, J., Wynn, P., Edwards, J., Jeffriess, H., and Kravitz, H. (1986). Clinical studies on the phenylethylamine hypothesis of affective disorder: Urine and blood phenylacetic acid and phenylalanine dietary supplements.J. Clin. Psychiat. 4766–70.

    Google Scholar 

  • Semba, J. I., Nankai, M., Maruyama, Y., Kaeno, S., Watanabe, A., and Takahashi, R. (1988). Increase in urinaryβ-phenylethylamine preceding the switch from mania to depression: A “rapid cycler.”J. Nerv. Ment. Dis. 176116–119.

    Google Scholar 

  • Szymanski, H. V., Naylor, E. W., and Karoum, F. (1987). Plasma phenylethylamine and phenylalanine in chronic schizophrenic patients.Biol. Psychiat. 22194–198.

    Google Scholar 

  • Urwyler, S., and Coward, D. (1987). Binding of [3H]-spiperone and [3H]-( − )-sulpiride to dopamine D2 receptors in rat striatal membranes: Methodological considerations and demonstration of the identical nature of the binding sites for the two ligands.Naunyn-Schmied. Arch. Pharmacol. 335115–122.

    Google Scholar 

  • Zhu, M.-Y., Juorio, A. V., Paterson, I. A., and Boulton, A. A. (1992). Regulation of aromatic L-amino acid decarboxylase by dopamine receptors in the rat brain.J. Neurochem. 58636–641.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurochemical Research Unit, Department of Psychiatry, University of Alberta, T6G 2B7, Edmonton, Alberta, Canada

    P. R. Paetsch & A. J. Greenshaw

Authors
  1. P. R. Paetsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. J. Greenshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paetsch, P.R., Greenshaw, A.J. Down-regulation ofβ-adrenergic and dopaminergic receptors induced by 2-phenylethylamine. Cell Mol Neurobiol 13, 203–215 (1993). https://doi.org/10.1007/BF00733750

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00733750

Key words

Search

Navigation