Ontogenic Changes of the Control by Phosphodiesterase-3 and -4 of 5-HT Responses in Porcine Heart and Relevance to Human Atrial 5-HT(4) Receptors

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2009 Jan 22

PMID 19154438

Citations 19

Authors

Alejandro Galindo-Tovar

Maria Luisa Vargas

Elisa Escudero

Alberto J Kaumann

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Atrial inotropic responses to 5-HT mediated through 5-HT(4) receptors fade, presumably through phosphodiesterase (PDE) activity. We investigated the influence of a selective inhibitor of PDE3 (cilostamide) or of PDE4 (rolipram) on the fade of 5-HT responses in atrial muscle.

Experimental Approach: 5-HT responses were compared, ex vivo, on sinoatrial beating rate of newborn piglets, porcine atrial and ventricular force, and human atrial force. cAMP levels were assessed in piglet atrium.

Key Results: 5-HT-evoked sinoatrial tachycardia did not fade and was not potentiated by cilostamide (300 nmol.L(-1)) or rolipram (1 micromol.L(-1)). Inotropic responses to 5-HT faded in atria from piglets, adolescent pigs and humans. Cilostamide reduced atrial fade of 5-HT responses in adolescent pigs and humans but not in newborn piglets. Cilostamide disclosed 5-HT ventricular responses in newborn, but not adolescent pigs. Rolipram reduced fade of atrial 5-HT responses in newborn and adolescent pigs but not in humans. Concurrent cilostamide + rolipram abolished fade of 5-HT responses in porcine left atria and facilitated ventricular 5-HT responses, but did not reduce residual fade in human atrium in the presence of cilostamide. 5-HT-evoked increases in cAMP faded; fade was abolished by concurrent cilostamide + rolipram.

Conclusions And Implications: PDE3-induced control of porcine 5-HT responses differed in atrium and ventricle and changed with age. PDE3 and PDE4 jointly prevented fade of inotropic and cAMP responses to 5-HT in porcine atrium. Unlike porcine atria, only PDE3 induced fade of 5-HT responses in human atria.

Citing Articles

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Neumann J, Hofmann B, Dhein S, Gergs U Int J Mol Sci. 2023; 24(5).

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Functional interaction of H-receptors and 5HT-receptors in atrial tissues isolated from double transgenic mice and from human patients.

Neumann J, Schwarzer D, Fehse C, Schwarz R, Marusakova M, Kirchhefer U Naunyn Schmiedebergs Arch Pharmacol. 2021; 394(12):2401-2418.

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Phosphodiesterases 2, 3 and 4 can decrease cardiac effects of H-histamine-receptor activation in isolated atria of transgenic mice.

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Dolce B, Christ T, Grammatika Pavlidou N, Yildirim Y, Reichenspurner H, Eschenhagen T Naunyn Schmiedebergs Arch Pharmacol. 2020; 394(2):291-298.

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Regulation of I and force by PDEs in human-induced pluripotent stem cell-derived cardiomyocytes.

Saleem U, Ismaili D, Mannhardt I, Pinnschmidt H, Schulze T, Christ T Br J Pharmacol. 2020; 177(13):3036-3045.

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