Article: Effects of 2-(2-pyridyl)ethylamine (PEA) on the isolated guinea-pig heart

The effect of 2-(2-pyridyl)ethylamine (PEA) on the rate and force of contraction of cardiac tissues from untreated and reserpine-pretreated guinea-pigs was examined. PEA produced changes in rate of spontaneously beating right atria without activation of H1 or H2-receptors. The positive chronotropic effect of PEA was eliminated when atria from reserpine-pretreated animals were used, indicating an entirely indirect mode of action of PEA in the right atrium. The positive inotropic effect of low doses of PEA in left atria was antagonized by promethazine, whereas the inotropic effect of higher doses of PEA was reduced either by propranolol or following reserpine pretreatment. In the right ventricle strip, the inotropic effect of high doses of PEA was blocked equally by propranolol and promethazine. The results obtained indicate that in the guinea-pig heart, PEA either produces it effects through catecholamine release (right atrium) or through a combination of both H1-receptor stimulation and catecholamine release (left atrium and right ventricle strip). The direct inotropic effects of PEA produced only small increases in force of contraction. The study indicates that caution should be used in ascribing all of the effects of PEA to histamine receptor stimulation.

Citing Articles

Function and Role of Histamine H Receptor in the Mammalian Heart.

Neumann J, Hofmann B, Kirchhefer U, Dhein S, Gergs U Pharmaceuticals (Basel). 2023; 16(5).

PMID: 37242517 PMC: 10223319. DOI: 10.3390/ph16050734.

The Roles of Cardiovascular H-Histamine Receptors Under Normal and Pathophysiological Conditions.

Neumann J, Kirchhefer U, Dhein S, Hofmann B, Gergs U Front Pharmacol. 2022; 12:732842.

PMID: 34987383 PMC: 8720924. DOI: 10.3389/fphar.2021.732842.

Histamine receptors in the lower esophageal sphincter (LES).

Coruzzi G, Bertaccini G Agents Actions. 1982; 12(1-2):157-61.

PMID: 7080951 DOI: 10.1007/BF01965131.

H1- and H2-receptors in the guinea-pig heart: an electrophysiological study.

Amerini S, Franconi F, Ledda F, Mantelli L, Mugelli A Agents Actions. 1982; 12(1-2):131-8.

PMID: 7080948 DOI: 10.1007/BF01965123.

On the presence of H1-receptors in various sections of guinea-pig heart: a correlation between binding and functional studies.

Bennardini F, Amerini S, Franconi F, Ledda F, Mantelli L, Matucci R Agents Actions. 1984; 15(3-4):167-71.

PMID: 6524516 DOI: 10.1007/BF01972344.

References

1.

CHENOWETH M, KOELLE E . An isolated heart perfusion system adapted to the determination of nongaseous metabolities; with sample data upon the isolated monkey heart. J Lab Clin Med. 2010; 31:600-8. View

2.

Flynn S, Gristwood R, Owen D . Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine in the isolated working heart of the guinea-pig. Br J Pharmacol. 1979; 65(1):127-37. PMC: 1668480. DOI: 10.1111/j.1476-5381.1979.tb17341.x. View

3.

Ash A, SCHILD H . Receptors mediating some actions of histamine. Br J Pharmacol Chemother. 1966; 27(2):427-39. PMC: 1510832. DOI: 10.1111/j.1476-5381.1966.tb01674.x. View

4.

McNeill J, Verma S . Histamine receptors in rabbit heart. Proc West Pharmacol Soc. 1978; 21:99-101. View

5.

Trendelenburg U . The action of histamine and 5-hydroxytryptamine on isolated mammalian atria. J Pharmacol Exp Ther. 1960; 130:450-60. View

6.

Tenner Jr T, McNeill J . Characterization of the inotropic response induced by stimulation of beta-adrenergic and H1 histaminergic receptors in guinea pig left atria. Can J Physiol Pharmacol. 1978; 56(6):926-33. DOI: 10.1139/y78-147. View

7.

Reinhardt D, Wagner J, SCHUMANN H . Differentiation of H1- and H2-receptors mediating positive chrono- and inotropic responses to histamine on atrial preparations of the guinea-pig. Agents Actions. 1974; 4(4):217-21. DOI: 10.1007/BF01965222. View

8.

Steinburg M, Holland D . Separate receptors mediating the positive inotropic and chronotropic effect of histamine in guinea-pig atria. Eur J Pharmacol. 1975; 34(1):95-104. DOI: 10.1016/0014-2999(75)90229-0. View

9.

Broadley K, Wilson C . The biphasic inotropic response of guinea-pig isolated atria to histamine receptor agonists [proceedings]. Br J Pharmacol. 1978; 64(3):387P-388P. PMC: 1668545. View

10.

van Rossum J . Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963; 143:299-330. View

11.

Verma S, McNeill J . Cardiac histamine receptors: differences between left and right atria and right ventricle. J Pharmacol Exp Ther. 1977; 200(2):352-62. View

Effects of 2-(2-pyridyl)ethylamine (PEA) on the Isolated Guinea-pig Heart