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Related Experiment Videos

Non-cyclic AMP-dependent, positive inotropic cyclodepsipeptides with negative chronotropy.

A Tsunoo1, M Kamijo

  • 1Meiji Institute of Health Science, Meiji Milk Products Co., Ltd., Odawara, Kanagawa, Japan.

The Journal of Pharmacology and Experimental Therapeutics
|August 24, 1999
PubMed
Summary

Natural cyclodepsipeptides (CDPs) like roseotoxin B and roseocardin increase cardiac muscle contraction force. These compounds exhibit positive inotropic and negative chronotropic effects, independent of cyclic AMP pathways.

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Area of Science:

  • Pharmacology
  • Cardiovascular Physiology
  • Natural Products Chemistry

Background:

  • Cyclodepsipeptides (CDPs) are a class of natural products with diverse biological activities.
  • The cardiac effects of many CDPs remain incompletely understood.
  • This study investigates novel CDPs, including roseocardin, for their impact on cardiac function.

Purpose of the Study:

  • To examine the in vitro effects of natural cyclodepsipeptides (CDPs) on isolated rat cardiac tissue.
  • To characterize the inotropic and chronotropic effects of destruxin A, destruxin B (DB), roseotoxin B (RB), and roseocardin (RC).
  • To elucidate the potential mechanisms underlying these cardiac effects.

Main Methods:

  • Isolated rat cardiac tissue preparations (right atrium, papillary muscles, trabecular muscles) were used.

Related Experiment Videos

  • Concentration-response curves were generated for CDPs ranging from 0.6 to 600 microM.
  • Effects on contraction force, relaxation time, atrial contraction intervals, and cellular signaling pathways (cyclic AMP, Na(+),K(+)-ATPase) were assessed.

    • Main Results:

    • RB, destruxin A, DB, and RC demonstrated a concentration-dependent increase in cardiac muscle contraction force.
    • RC slightly prolonged relaxation time, while RB, destruxin A, and DB did not.
    • These effects were independent of cyclic AMP levels and various receptor antagonists, suggesting a non-cyclic AMP-dependent mechanism.

    Conclusions:

    • Natural CDPs, including RB and RC, exert significant positive inotropic effects on cardiac muscle.
    • These compounds also exhibit negative chronotropic effects, as indicated by prolonged atrial contraction intervals.
    • The observed cardiac effects are mediated through non-cyclic AMP-dependent pathways.