Intracellular signaling in vascular smooth muscle.
The two major modalities of pharmacomechanical coupling, inositol 1,4,5, trisphosphate induced Ca2+ release and modulation of Ca(2+)-sensitivity, are reviewed. Recent studies show that although changes in cytoplasmic Ca2+ play the major role in regulating smooth muscle contraction, agonists can also significantly affect the contractile state by modifying Ca(2+)-sensitivity. Inhibition of myosin light chain kinase or myosin light chain phosphatase leads to, respectively, desensitization or sensitization of the contractile apparatus to Ca2+. G-protein linked inhibition of myosin light chain phosphatase and Ca2+ release mediated by the phosphatidylinol cascade are the two major pharmacomechanical coupling mechanisms.
Somlyo
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AV
Department of Pathology and Molecular Physiology and Biological Physics, University of Virginia, Charlottesville 22908.
Somlyo
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AP
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*
D015544:Inositol 1,4,5-Trisphosphate; D009219:Myosin-Light-Chain Kinase; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium