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Beta-adrenergic agonists and cyclic AMP decrease intracellular resting free-calcium concentration in ileum smooth

I Parker, Y Ito, H Kuriyama

    Proceedings of the Royal Society of London. Series B, Biological Sciences
    |March 23, 1987
    PubMed
    Summary
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    Beta-adrenergic agonists relax visceral smooth muscle by decreasing intracellular free-calcium levels. This effect is mediated by increased cyclic AMP, lowering both resting and stimulated calcium concentrations.

    Area of Science:

    • Pharmacology
    • Physiology
    • Cell Biology

    Background:

    • Visceral smooth muscle relaxation is crucial for physiological function.
    • Beta-adrenergic agonists are known to induce relaxation in smooth muscle.
    • The precise mechanisms underlying this relaxation, particularly calcium handling, require further elucidation.

    Purpose of the Study:

    • To investigate the effect of beta-adrenergic agonists on intracellular free-calcium levels in guinea-pig ileum.
    • To determine the role of cyclic AMP in mediating these calcium changes.
    • To understand the contribution of altered calcium homeostasis to smooth muscle relaxation.

    Main Methods:

    • Measurement of intracellular free-calcium concentrations using fura-2 in guinea-pig ileum smooth muscle strips.

    Related Experiment Videos

  • Application of isoprenaline, forskolin, and dibutyryl cyclic AMP.
  • Electrical field stimulation to induce muscle activity and calcium transients.

    • Main Results:

    • Resting intracellular calcium levels were approximately 180 nM, rising to 300-400 nM upon stimulation.
    • Isoprenaline significantly reduced resting calcium levels to ~130 nM and suppressed spontaneous calcium transients.
    • Elevating cyclic AMP levels with forskolin or dibutyryl cyclic AMP mimicked isoprenaline's effects on calcium levels.

    Conclusions:

    • Beta-adrenergic agonist-induced relaxation of visceral smooth muscle is partly mediated by a reduction in intracellular resting free-calcium.
    • This calcium reduction is linked to an increase in intracellular cyclic AMP levels.
    • The findings provide a mechanistic link between beta-adrenergic signaling, cyclic AMP, and calcium regulation in smooth muscle.