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Related Experiment Videos

Interaction between signal transduction pathways contributing to gallbladder tonic contraction

P Yu1, K M Harnett, P Biancani

  • 1Department of Medicine, Rhode Island Hospital, Providence.

The American Journal of Physiology
|December 1, 1993
PubMed
Summary

Cat gallbladder tone relies on intracellular calcium release and protein kinase C (PKC) activation. Diacylglycerol (DAG) and inositol trisphosphate (IP3) synergistically activate PKC, while calmodulin may inhibit this pathway.

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Area of Science:

  • Physiology
  • Cell Biology
  • Biochemistry

Background:

  • Gallbladder muscle tone is crucial for bile storage and release.
  • The precise molecular mechanisms underlying sustained gallbladder contraction (tone) are not fully elucidated.

Purpose of the Study:

  • To investigate the signaling pathways responsible for generating and maintaining cat gallbladder tone.
  • To determine the roles of calcium, protein kinase C (PKC), diacylglycerol (DAG), inositol trisphosphate (IP3), and calmodulin in gallbladder muscle contraction.

Main Methods:

  • Studied cat gallbladder muscle strips.
  • Utilized strontium to substitute for calcium.
  • Administered PKC inhibitor H-7 and calmodulin antagonist W-7.
  • Measured basal levels of DAG and IP3 in gallbladder and esophageal muscle.

Related Experiment Videos

  • Examined responses in single cells with varying doses of IP3 and DAG.

    • Main Results:

    • Strontium substitution and H-7 abolished gallbladder tone, indicating dependence on intracellular calcium and PKC.
    • W-7 had no effect on tone, suggesting a minimal role for calmodulin in basal tone.
    • Gallbladder muscle showed higher basal DAG and IP3 levels than esophageal muscle.
    • Low-dose IP3 potentiated DAG-induced contraction via PKC activation, blocked by H-7.
    • High-dose IP3-induced contraction was insensitive to H-7 but blocked by CGS-9343B.
    • DAG-induced contraction was inhibited by activated calmodulin.

    Conclusions:

    • The synergistic interaction between DAG and IP3-mediated calcium release likely activates PKC, contributing to gallbladder tone.
    • Activated calmodulin may act as an inhibitory regulator of the PKC pathway in gallbladder smooth muscle.