平滑筋の収縮制御に関する最近の進歩 : 創薬における薬理学の役割

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In this paper, we briefly review current topics about smooth muscle with regards to Ca2+ release, Ca2+ sensitization, and Ca2+ regulation of contraction. Inositol 1, 4, 5-trisphosphate releases Ca2+ from the sarcoplasmic reticulum, where Ca2+-dependent immediate feedback control may work. However, the involvement of this feedback control in the Ca2+-induced Ca2+ release mechanism remains to be elucidated. Either agonist or GTP γ S is known to increase the Ca2+ sensitivity of myofilaments. The agonist-induced Ca2+ sensitization could be explained by the up-regulation due to myosin light chain kinase or by the down-regulation due to myosin light chain phosphatase. The GTP γ S-induced Ca2+ sensitization seems to be mediated by rho A p21, a small G protein. Thus, myosin phosphorylation is not the obligatory way to regulate the actin-myosin interaction. We propose that cross-linking between actin and myosin may work as an alternative way to regulate the interaction from biochemical studies. The candidates for the cross-linkers are caldesmon, calponin and myosin light chain kinase. The inhibitory effect of Ca2+ on the interaction, which is observed under the specific conditions for measuring smooth muscle contraction, may hold the key to finding the physiological significance of the cross-linking activity.