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.