Essential Role of Newly Synthesized ATP for Cyclic GMP-Induced Relaxation in α-Toxin Permeabilized Smooth Muscle of Rat Proximal Colon

概要

論文の詳細を見る
The role of newly synthesized ATP in cyclic GMP-induced relaxation was studied in membrane-permeabilized longitudinal muscle preparations of the rat proximal colon. Cyclic GMP and 8-bromo cGMP induced concentration-dependent relaxation of α-toxin permeabilized preparations which were precontracted by 3μM Ca^<2+> in the presence of 4mM ATP and 5mM phosphocreatine (PC). The relaxation by 8-bromo cGMP was inhibited by Rp-8-pCPT-cGMPS, an inhibitor of cyclic GMP-dependent protein kinase. The relaxation was inhibited by removal of PC from the bating solution, in spite of the presence of ATP. The relaxation was also inhibited by dinitrofluorobenzene (DNFB), a selective inhibitor of creatine kinase. The removal of PC or treatment with DNFB is known to produce accumulation of ADP within smooth muscle cell, however, ADP_βS did not affect the relaxation. After irreversible inhibition of endogenous creatine kinase by DNFB in β-escin permeabilized preparations, treatment of the preparations with exogenous creatine kinase restored the relaxation. In the presence of ADP and PC but without ATP, 8-bromo cGMP induced the relaxation to the similar extent to that in the presence of ATP and PC. These results suggest that ATP newly synthesized from ADP and PC by creatine kinase is essential for cyclic GMP-induced relaxation of the smooth muscle preparations obtained from the proximal colon of rats.
日本平滑筋学会の論文