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

抄録

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.