Is guanosine-5'-triphosphate involved in calcium-activation of contractile proteins in vascular smooth muscle?
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 beta-escin. The Ca2+ sensitivity assessed by the EC50 value for the Ca2+ (0.1-100 microM)-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 microM); 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 (GDP beta S, 100 microM) significantly decreased the Ca2+ sensitivity with the 1st Ca2+ application and eliminated the run-down of Ca2+ sensitivity. GTP (3-150 microM), 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 (GTP gamma S) and reversed by GDP beta S (100 microM). 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 Ca(2+)-activation of contractile proteins.
Akata
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Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Boyle
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D000818:Animals; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D003285:Contractile Proteins / Q000187:drug effects*; D004928:Escin / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015220:Calcium Channels; D003285:Contractile Proteins; D006153:Guanosine Diphosphate; D004928:Escin; D006160:Guanosine Triphosphate; D002118:Calcium