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Related Experiment Videos

A 5-hydroxytryptamine receptor in human atrium.

A J Kaumann1, L Sanders, A M Brown

  • 1Smith Kline Beecham Pharmaceuticals, The Frythe, Welwyn, Hertfordshire.

British Journal of Pharmacology
|August 1, 1990
PubMed
Summary

Serotonin (5-HT) enhances atrial contraction and relaxation, acting via a mechanism similar to the 5-HT4 receptor. Its effects are independent of beta-blockers and mediated by cyclic AMP signaling pathways.

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Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor knockout mice. Obligatory role of beta1-adrenoceptors for putative beta4-adrenoceptor pharmacology.

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Area of Science:

  • Pharmacology
  • Cardiovascular Physiology

Background:

  • Beta-adrenoceptor blocking agents are commonly used in cardiovascular medicine.
  • The role of serotonin (5-hydroxytryptamine, 5-HT) in human atrial function, particularly in patients on beta-blockers, requires further elucidation.

Purpose of the Study:

  • To investigate the effects of 5-hydroxytryptamine (5-HT) on human right atrial appendages from patients treated with beta-adrenoceptor blocking agents.
  • To characterize the receptor subtype and signaling pathways involved in 5-HT's inotropic and chronotropic actions in the human atrium.

Main Methods:

  • Isometric tension recordings of human atrial strips.
  • Assessment of contractile force and relaxation kinetics.
  • Pharmacological blockade studies using various receptor antagonists.

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  • Measurement of intracellular cyclic adenosine monophosphate (cyclic AMP) levels and protein kinase activity.

    • Main Results:

    • 5-HT significantly increased contractile force and accelerated relaxation, effects comparable to (-)-isoprenaline.
    • These effects were resistant to blockade by several beta-adrenoceptor antagonists and other receptor blockers, but competitively antagonized by ICS 205930.
    • 5-HT potentiated the effects of cocaine and was approximately five times more potent than (-)-noradrenaline inotropic effects.
    • 5-HT increased cyclic AMP levels and cyclic AMP-dependent protein kinase activity, suggesting a role for cyclic AMP-dependent phosphorylation.

    Conclusions:

    • The human atrial 5-HT receptor mediating inotropic effects shares characteristics with the neuronal 5-HT4 receptor.
    • The inotropic effects of 5-HT in the human atrium are mediated via a cyclic AMP-dependent pathway, involving phosphorylation of Ca2+ channels and contractile proteins.
    • These findings are relevant for understanding serotonin's role in cardiac function, especially in patients receiving beta-blocker therapy.