Signal transduction pathways mediating CCK-induced gallbladder muscle contraction.

Abstract

The signal transduction that mediates CCK-induced contraction of gallbladder muscle was investigated in the cat. Contraction was measured by scanning micrometry in single muscle cells isolated enzymatically with collagenase. Production of D-myo-inositol 1,4, 5-trisphosphate (IP3) and sn-1,2-diacylglycerol (DAG) was quantitated using HPLC and TLC, respectively. Protein kinase C (PKC) activity was determined by measuring the phosphorylation of a specific substrate peptide from myelin basic protein, Ac-MBP-(4-14). CCK-induced contraction was blocked by incubation in strontium medium, pertussis toxin (PTx), and antibodies against Gialpha3 or betagamma-subunits but was not blocked by Ca2+-free medium or by antibodies against Gq/11alpha, Gialpha1-2, or Goalpha. The contraction induced by CCK was inhibited by the phospholipase C (PLC) inhibitor U-73122, anti-PLC-beta3 antibody, and the IP3 receptor antagonist heparin but was not inhibited by the the phospholipase D inhibitor propranolol or antibodies against PLC-beta1 or PLC-beta2. Western blot analysis of gallbladder muscle revealed the presence of PLC-beta2 and PLC-beta3 but not PLC-beta1. CCK caused a 94% increase in IP3 generation and an 86% increase in DAG generation. A low dose of CCK caused PKC translocation, and CCK-induced contraction was blocked by the PKC inhibitor H-7. A high dose of CCK, however, caused no PKC translocation, and its contraction was blocked by the calmodulin antagonist CGS9343B. In conclusion, CCK contracts cat gallbladder muscle by stimulating PTx-sensitive Gi 3 protein coupled with PLC-beta3, producing IP3 and DAG. Low doses activate PKC, whereas high doses activate calmodulin.

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@article{Yu1998SignalTP, title={Signal transduction pathways mediating CCK-induced gallbladder muscle contraction.}, author={Paul Chuan-Wei Yu and Q. Chen and Zhuopeng Xiao and Karen M Harnett and Piero Biancani and Jos{\'e} Behar}, journal={The American journal of physiology}, year={1998}, volume={275 2 Pt 1}, pages={G203-11} }