Regulation of vascular smooth muscle contraction. The roles of Ca2+, protein kinase C and myosin light chain phosphatase.
Vasoconstrictors bind to their receptors on the cell surface to active phospholipase C and Ca2+ channels, resulting in the mobilization of Ca2+ from intracellular are extracellular Ca2+ pools and protein kinase C activation. Vasoconstrictors are also thought to activate a distinct cellular mechanism for downregulating 20 kDa myosin light chain (MLC20) phosphatase activity, which involves Rho p21 and protein kinase C, resulting in an increase in the Ca2+ sensitivity of MLC20 phosphorylation. Protein kinase C also appears to activate a MLC20 phosphorylation-independent mechanism for contraction, contributing to the maintenance of agonist-induced contraction. On the other hand, vasorelaxants inhibit activation of phospholipase C and gating of Ca2+ channels, or stimulate Ca2+ extrusion across the plasma membrane, leading to a decrease in the [Ca2+]i. Vasorelaxants also appear to stimulate MLC20 phosphatase activity, resulting in a further reduction of contractile response. The modulatory mechanism for changing the Ca2+ sensitivity, together with the major regulatory mechanism for cellular Ca2+ metabolism, plays an important role in regulating vascular smooth muscle tone.
Takuwa
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Department of Cardiovascular Biology, Faculty of Medicine, University of Tokyo, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D009119:Muscle Contraction / Q000502:physiology*; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D043263:Myosin-Light-Chain Phosphatase; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D020741:rho GTP-Binding Proteins
D015220:Calcium Channels; D000242:Cyclic AMP; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium