Abstract
Smooth muscle from gallbladders with cholesterol stones exhibits impaired response to cholecystokinin (CCK). This study investigated whether the impaired response is mediated by different signal-transduction pathways responsible for CCK-induced contraction in prairie dog and human gallbladders with cholesterol stones. Gallbladder muscle cells were isolated enzymatically to study contraction. Protein kinase C (PKC) activity was measured by examining the phosphorylation of a specific substrate peptide from myelin basic protein Ac-MBP-(4-14). Gallbladder muscle cells from high-cholesterol- fed prairie dogs contracted less in response to CCK octapeptide (CCK-8) than those from the control group. However, inositol-1,4,5-trisphosphate (IP3), diacylglycerol, and guanosine 5'-O-(3-thiotriphosphate) induced the same magnitudes of contraction in these two groups. In control prairie dog and human gallbladders, the maximal contraction caused by 10-8 M CCK-8 was blocked by the calmodulin antagonist CGS9343B but not by the PKC inhibitor H- 7. Conversely, in gallbladders with cholesterol stones from prairie dogs or human patients, the maximal contraction induced by 10-8 M CCK-8 was blocked by H-7 and chelerythrine but not by CGS9343B. In these gallbladders CCK-8 caused a significant PKC translocation from the cytosol to the membrane. High CCK concentrations may activate the calmodulin-dependent pathway in functionally normal gallbladder muscle and the PKC-dependent pathway in muscle from gallbladders with cholesterol stones. The defect of gallbladder muscle after cholesterol feeding and stones might reside in the steps before G protein activation.
Original language | English (US) |
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Pages (from-to) | G838-G844 |
Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 272 |
Issue number | 4 35-4 |
DOIs | |
State | Published - Apr 1997 |
Externally published | Yes |
Keywords
- calmodulin
- cholesterol stones
- protein kinase C
- smooth muscle
ASJC Scopus subject areas
- Physiology
- Hepatology
- Gastroenterology
- Physiology (medical)