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+ (0.1-100 μM)-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. Guanosine-5'-(2-O-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 Ca2+ contractions in their later stage; its latter effect was mimicked by guanosine-5'-(3-O-thio) triphosphate (GTPγS) and reversed by GDPβS (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.
- Gtp-binding protein (G-protein)
- Guanosine-5'-triphosphate (GTP)
- Myofilament Ca sensitivity
- Vascular smooth muscle