GTP-binding protein regulates the contractile response elicited by the phorbol ester (PMA)-induced activation of protein kinase C in the isolated rat aorta.
1. The aim of the present study was to investigate the involvement of GTP-binding protein in the contractile response induced by activation of protein kinase C (PKC) in isolated rat aorta. The rats were treated with islet-activating protein (IAP) for 4 days prior to the experiments. 2. In the aorta from control rats, phorbol 12-myristate 13-acetate (PMA) produced biphasic contractions; twitch contraction superimposed on the slowly developing contraction. The twitch contraction was abolished by the removal of external Ca2+ or by treatment with nicardipine. In the aorta pretreated with IAP, PMA produced only a slowly developing contraction, and no twitch contraction was induced. 3. The application of Ca2+ to aortic strips in a Ca(2+)-free solution, that had been treated with 10(-6) M PMA caused concentration-dependent contraction, and the contraction was completely inhibited by IAP. 4. Pretreatment with IAP inhibited Ca(2+)-induced contraction of the aorta in Ca(2+)-free medium in the presence of 10(-6) M clonidine, but did not affect the Ca(2+)-induced contraction in the medium treated with 10(-6) M phenylephrine and 10(-7) M nicardipine. 5. These results suggest that the activation of PKC by PMA produces biphasic contractions in the rat aorta. The twitch contraction may be induced by the activation of voltage-dependent Ca(2+)-channels and the activation may be regulated by IAP-sensitive GTP-binding protein.
Department of Pharmacology, Urjohn Research Laboratories, Ibahaki, Japan.
H
H
Suenaga
Y
Y
Kasuya
K
K
Kamata
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium