Direct effect of phenylethylamine upon isolated rat aortic strip

doi:10.1016/0014-2999(80)90433-1

European Journal of Pharmacology

Volume 63, Issues 2–3, 2 May 1980, Pages 95-101

https://doi.org/10.1016/0014-2999(80)90433-1 Get rights and content

Abstract

Phenylethylamine (PEA) has been implicated in a number of central and peripheral nervous system disorders. Its possible mechanisms of action include stimulation via catecholamine release and direct stimulation by PEA. We have examinekd the effects of PEA on isolated vascular smooth muscle (VSM) to further explore the mechanism by which PEA produces contraction in this tissues. Helical strips of rat oarta were suspended in a muscle bath. Smooth muscle contractions were recorded via force transducer. PEA elicited a concentration dependent contraction from these strips with a threshold near 10⁻⁶ M and a maximum response at 5 × 10⁻³ M. Pretreatment of rats with reserpine dramatically reduced the norepinerphrine (NE) content of kidney, heart and spleen of these animals but did not prevent the action of PEA on VSM. The presence of phentolamine (10⁻⁴ M) completely blocked the strip response to PEA. The presence of propranolol (10⁻⁷ or 10⁻⁴ M) altered but did not block the VSM response to PEA. These results argue that the effect of PEA upon the aortic strip preparation involve a direct action of this amine upom VSM.

References (34)

S.A. Antelman et al.
Phenylethylamine: Evidence for a direct, post-synaptic dopamine-receptor stimulating action
Brain Res.
(1977)
R.J. Baldessarini et al.
Trace amines and alternative neurotransmitters in the central nervous system
Biochem. Pharm.
(1978)
R.L. Borison et al.
Brain 2-phenylethylamine as a mediator for the central actions of amphetamine and methylphenidate
Life Sci.
(1975)
J.C. David et al.
On the importance of decarboxylation in the metabolism of phenylalanine, tyrosine and trytophan
Arch. Biochem. Biophys.
(1974)
D.J. Edwards et al.
Phenylethylamine in brain function and dysfunction: Neurochemical and pharmacological studies
J.E. Fischer et al.
Neurotransmitters and hepatic failure
Lancet
(1971)
W.J. Giardina et al.
Iontophoretic study of the effects of norepinephrine and 2-phenylethylamine on single cortical neurons
Life Sci.
(1973)
D.M. Jacobowitz et al.
Method for the rapid determination of norepinephrine, dopamine, and serotonin in the same brain region
Pharm. Biochem. Behav.
(1978)
R. Silkaitis et al.
Pathways linking L-phenylalanine and 2-phenylethylamine with p-tyramine in rabbit brain
Brain Res.
(1976)
B. Bhagat et al.
Factors influencing the depletion of cardiac norepinephrine by tyramine
J. Pharmacol. Exp. Ther.
(1966)

A.A. Boulton

Cerebral arylalkyl aminergic mechanisms, 1976

B.A. Faraj et al.

Tyramine and liver disease

J. Feldman et al.

The nature of the interaction of amines with the pancreatic beta cell to influence insulin secretion

J. Pharmacol. Exp. Ther.

(1971)

F. Franzen et al.

Biologically Active Amines Found in Man

(1969)

W.J. Giardina

Analgesic properties of phenyl-ethylamine and phenylethanolamine in mice

Pharmacology

(1974)

I.J. Kopin

False adrenergic transmitters

Ann. Rev. Pharm.

(1968)

M.F. Mason

β-Phenylethylamine: Factors regulating its concentration and distribution in blood

Cited by (19)

β-Phenylethylamine-Class Trace Amines in Neuropsychiatric Disorders: A Brief Historical Perspective
2016, Trace Amines and Neurological Disorders: Potential Mechanisms and Risk Factors
β-Phenylethylamine provides the basic chemical structure for an extensive number of endogenous and exogenous bioactive compounds. Many already used for their medicinal effects, and others consumed for recreational purposes or advertised for various other “effects.” for example, weight-loss adjuvants, memory, and general performance enhancers.
β-Phenylethylamine is also the parent compound of a group of endogenous amines commonly known as trace amines to emphasize their low plasma and tissue levels relative to those observed for the classical neurotransmitter amines. Currently, the general name for trace amines has been expanded to include a growing number of exogenous biologically active amines showing wide differences in chemical structure as well as behavioral and pharmacological profile.
Following recent advances in genetic and molecular biology, particularly after the discovery of trace amine-associated receptors, studies on the role of trace amines in various neuropsychiatric disorders have been expanded to include drug abuse, obesity, and type 2 diabetes mellitus.
We now discuss preliminary data on the pharmacological and behavioral profile of various novel monomethylated and monohalogenated phenylethylamine derivatives. We hope this work will lead to the rational design of newer, safer, and effective medications for neuropsychiatric and metabolic disorders.
Characterization of β-phenylethylamine-induced monoamine release in rat nucleus accumbens: A microdialysis study
1998, European Journal of Pharmacology
In vivo microdialysis was used to investigate the effect of β-phenylethylamine on extracellular levels of monoamines and their metabolites in the nucleus accumbens of conscious rats. At all doses tested (1, 10 and 100 μM), infusion of β-phenylethylamine through the microdialysis probe significantly increased extracellular levels of dopamine in the nucleus accumbens. These increases were dose-related. The increase in dopamine levels induced by 100 μM β-phenylethylamine was not affected by co-perfusion of 4 μM tetrodotoxin. The ability of 100 μM β-phenylethylamine to increase the extracellular level of dopamine was comparable to that of the same dose of methamphetamine. On the other hand, β-phenylethylamine had a much less potent enhancing effect on 5-hydroxytryptamine (5-HT) than dopamine levels. Only the highest dose (100 μM) caused a statistically significant effect on 5-HT levels. Over the dose range tested (1, 10 and 100 μM), β-phenylethylamine had no effect on extracellular metabolite levels of dopamine and 5-HT. The results suggest that β-phenylethylamine increases the efflux of monoamines, preferentially dopamine, without affecting monoamine metabolism, in the nucleus accumbens.
Antagonistic effects of β-phenylethylamine on quinpirole- and (-)-sulpiride-induced changes in evoked dopamine release from rat striatal slices
1998, European Journal of Pharmacology
To assess the role of β-phenylethylamine in aspects of dopamine release, we measured the level of β-phenylethylamine in the rat striatum after killing the rats by microwave irradiation. We then investigated the effect of β-phenylethylamine on electrically evoked dopamine release from rat striatal slices in vitro. The striatal β-phenylethylamine level was 46.5±3.5 ng/g wet tissue, equivalent to 0.3 μmol/l. Superfusion with low concentrations of β-phenylethylamine up to 1 μmol/l had no effect on spontaneous or electrically evoked dopamine release from striatal slices. Quinpirole reduced the evoked dopamine release from slices in a concentration-dependent manner. The quinpirole-induced reduction of evoked dopamine release was attenuated 30% by superfusion with 0.3 μmol/l β-phenylethylamine. Moreover, the (−)-sulpiride (0.1 μmol/l)-induced increase in evoked dopamine release was also attenuated by superfusion with 0.3 μmol/l β-phenylethylamine. These data indicate that submicromolar levels of β-phenylethylamine could modify the dopamine autoreceptor mediated changes in evoked dopamine release from rat striatal slices.
Characteristics of Antinociception Induced by Noncatecholic Phenylethylamine Derivatives: The Involvement of Alpha-2-Adrenoceptors
1993, The Japanese Journal of Pharmacology
Characteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, β-phenylethylamine (PEA) and β-hydroxyphenylethylamine (OHPEA), were examined. The antinociception induced by PEA derivatives was enhanced by intracisternal injection of norepinephrine or clonidine and attenuated by intracisternal injection of phentolamine or yohimbine, but was not affected by intracisternal injection of prazosin in the mouse hot plate method. PEA derivatives induced a contraction of the rat vas deferens, and this contraction by PEA derivatives was attenuated by the application of phentolamine. The contractions induced by PEA or OHPEA in the reserpinized vas deferens were much smaller than those in the normal one. PEA derivatives inhibited the electrical stimulation-evoked contractions of the vas deferens, and the inhibition by PEA derivatives was reversed by the application of yohimbine. These findings indicate that PEA derivatives may induce the antinociception as a result of stimulating the α₂-adrenoceptors. The stimulation of α₂-adrenoceptors by PEA derivatives may result from the release of endogenous norepinephrine and/or from direct action on the α₂-adrenoceptors.
Release of some endogenous trace amines from rat striatal slices in the presence and absence of a monoamine oxidase inhibitor
1989, Life Sciences
The basal and 50 mM K⁺-stimulated release of $m$ -tyramine (mTA), $p$ -tyramine (pTA), tryptamine (TR) and phenylethylamine (PE) from striatal slices obtained from rats pretreated with a monoamine oxidase inhibitor (MAOI) was investigated. A K⁺-stimulated release of mTA and pTA was observed, but K⁺ did not stimulate either TR or PE release. The latter two amines, therefore, are unlikely to be conventional neurotransmitters in the rat striatum. The release of endogenous striatal pTA from control rats was also investigated. Veratridine stimulated endogenous pTA release, but 50 mM K⁺ did not. It is possible, therefore, that endogenous pTA can be release iin a transmitter-like fashion.
Examination of the bronchoconstrictor response of guinea-pig isolated lung to β-phenylethylamine
1985, General Pharmacology
- 1.
  1. β-Phenylethylamine (PEA) produced a contraction of the guinea-pig isolated lung parenchymal strip and bronchoconstriction of perfused lungs.
- 2.
  2. Reserpine pretreatment had little effect on these responses indicating a substantial direct effect.
- 3.
  3. Phentolamine (10⁻⁶ and 10⁻⁵M) had minimal effect on PEA in the lung strip compared with that on noradrenaline, eliminating involvement of α-adrenoceptors.
- 4.
  4. PEA was unaffected by atropine (10⁻⁷M) or a mepyramine (10⁻⁷M); metiamide (10⁻⁴M) mixture. The contraction was not therefore mediated via muscarinic or histaminergic receptors. 5-HT and dopamine receptors were also discounted.
- 5.
  5. Possible stimulation of a phenylethylaminergic receptor and its relevance to bronchial asthma is discussed.

View all citing articles on Scopus

View full text

Direct effect of phenylethylamine upon isolated rat aortic strip

Abstract

Brain Res.

Biochem. Pharm.

Life Sci.

Arch. Biochem. Biophys.

Lancet

Life Sci.

Pharm. Biochem. Behav.

Brain Res.

Factors influencing the depletion of cardiac norepinephrine by tyramine

J. Pharmacol. Exp. Ther.

Cerebral arylalkyl aminergic mechanisms, 1976

Tyramine and liver disease

The nature of the interaction of amines with the pancreatic beta cell to influence insulin secretion

J. Pharmacol. Exp. Ther.

Biologically Active Amines Found in Man

Analgesic properties of phenyl-ethylamine and phenylethanolamine in mice

Pharmacology

False adrenergic transmitters

Ann. Rev. Pharm.

β-Phenylethylamine: Factors regulating its concentration and distribution in blood