Is Guanosine-5'-triphosphate Involved in Calcium-Activation of Contractile Proteins in Vascular Smooth Muscle?&dagger

[摘要] References(37)Cited-By(4)Isometric tension was measured to investigate the effects of guanosine-5''-triphosphate (GTP) on the run-down of myofilament Ca2+ sensitivity in isolated rat mesenteric arteries permeabilized with β-escin. The Ca2+ sensitivity assessed by the EC50 value for the Ca2+ (0.1-100μM)-tension relationship progressively runs down in the control strips, while it was well-preserved for 5-successive Ca2+ applications in the presence of GTP (50 μM); no significant difference was found in the Ca2+ sensitivity observed with the 1st Ca2+ application between the control and GTP-treated strips. Guano sine-5''-(2-Ο-thio) diphosphate (GDPβS, 100 μM) significantly decreased the Ca2+ sensitivity with the 1st Ca2+ application and eliminated the run-down of Ca2+ sensitivity. GTP (3 -150 μM), applied to the strips submaximally precontracted with Ca2+, had a little effect on the Ca2+ contractions in the early stage of experiments, but dramatically enhanced the Ca 2+ contractions in their later stage; its latter effect was mimicked by guanosine-5''-(3-Ο-thio) triphosphate (GTPγS) and reversed by GDP13S (100 μM). The results suggest: 1) loss of endogenous GTP following permeabilization is involved in the run-down of Ca2+ sensitivity; and 2) activation of G-proteins is involved in Ca2+-activation of contractile proteins.

[学科分类] 药理学

[关键词] Guanosine-5'-triphosphate (GTP);GTP-binding protein (G-protein);Myofilament Ca2+ sensitivity;Membrane-permeabilization;Vascular smooth muscle