Ras proteins increase Ca(2+)-responsiveness of smooth muscle contraction.
G-proteins may be involved in receptor-mediated Ca(2+)-sensitization of smooth muscle contraction, but the responsible G-proteins are not yet known. Here we show that in beta-escin skinned mesenteric microarteries, H-ras p21 proteins, preactivated with GTP or GTP gamma S, increase force at constant submaximal Ca2+ (pCa 6.3) concentration dependently. The GTP-bound form of the wild-type H-ras p21 and the oncogenic mutant (p21[G12V]) were equally effective. The nucleotide-free and the inactive GDP-bound form of ras p21 had no effect on force. The tryosine kinase inhibitor, tryphostin, partially reversed the effect of the ras proteins in the GTP-bound form on force. Thus, ras proteins mimic the Ca(2+)-sensitizing effect of GTP gamma S and vasoconstrictors in mesenteric microarteries which may involve tyrosine phosphorylation.
II. Physiologisches Institut, Universität Heidelberg, Germany.
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S
Satoh
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Rensland
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Pfitzer
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D004928:Escin; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D008643:Mesentery / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras) / Q000494:pharmacology*
D011518:Proto-Oncogene Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004928:Escin; D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras); D002118:Calcium