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Related Experiment Videos

Progesterone inhibits gallbladder motility through multiple signaling pathways.

L W Kline1, E Karpinski

  • 1Department of Physiology, University of Alberta, Edmonton, Alta., Canada T6G 2H7. lkline@ualberta.ca

Steroids
|May 27, 2005
PubMed
Summary

Progesterone (P) relaxes gallbladder smooth muscle, potentially explaining pregnancy-related biliary stasis. This study shows P rapidly inhibits gallbladder motility through nongenomic pathways involving tyrosine kinase and PKA/cAMP signaling.

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Area of Science:

  • Gastroenterology
  • Endocrinology
  • Pharmacology

Background:

  • Progesterone (P) inhibits gastrointestinal smooth muscle contractility.
  • Elevated progesterone during pregnancy can lead to biliary stasis, characterized by reduced gallbladder emptying.
  • This study investigates the mechanisms of progesterone's effect on gallbladder motility.

Purpose of the Study:

  • To investigate the effect of progesterone and its metabolites on guinea pig gallbladder contraction.
  • To elucidate the signaling pathways mediating progesterone's inhibitory effect on gallbladder smooth muscle.

Main Methods:

  • Guinea pig gallbladder strips were precontracted with cholecystokinin octapeptide (CCK).
  • The effects of progesterone, nifedipine, and various inhibitors (PKA, PKG, tyrosine kinase, IP3) on CCK-induced contraction and progesterone-induced relaxation were assessed.

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  • Calcium (Ca2+) was substituted with strontium (Sr2+) to assess calcium's role.

    • Main Results:

    • Progesterone induced concentration-dependent relaxation of gallbladder strips.
    • Progesterone pretreatment reduced CCK-induced tension, an effect mimicked by nifedipine.
    • Inhibitors of PKA/cAMP, PKG, tyrosine kinase, and IP3-induced Ca2+ release significantly reduced progesterone's relaxation effect.
    • Calcium substitution with strontium reduced CCK-induced tension.

    Conclusions:

    • Progesterone rapidly inhibits gallbladder motility through nongenomic mechanisms.
    • Signaling pathways involving tyrosine kinase and PKA/cAMP activity mediate progesterone's effect on gallbladder contractility.
    • These findings provide insight into the physiological regulation of gallbladder function and pregnancy-related biliary stasis.