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- _8 value "FIG. 11. Proposed mechanism of regulation of smooth muscle contraction via inhibition of MLCP via the RhoA/ROK pathway and phosphorylation of myosin by ILK. Contractile agonists such as endothelin-1, angiotensin II, and vasopressin act via receptors that are coupled to both Gq/11 and G12/13 heterotrimeric G proteins (43). Gq/11 activates phospholipase Cb (PLCb), which hydrolyzes phosphatidylinositol 4,5- bisphosphate (PIP2) to generate inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol. Inositol 1,4,5-trisphosphate diffuses to the sarcoplasmic reticulum (SR), where it interacts with the inositol 1,4,5-trisphosphate receptor, a Ca21 release channel in the sarcoplasmic reticulum membrane, thereby triggering Ca21 release from the sarcoplasmic reticulum. The increase in [Ca21]i activates CaM-dependent MLCK and cross-bridge cycling." provenance.