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

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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.
社団法人日本薬理学会の論文
1997-09-01