Roles of protein kinase C on the mechanical activity of vascular smooth muscles.
We investigated the role of protein kinase C in the mechanical responses evoked by high K or by acetylcholine (ACh) in intact vascular smooth muscle tissues, and by Ca in skinned vascular smooth muscle tissues. To activate protein kinase C, the phorbol ester 12-o-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, or 1,2-diolein, plus phosphatidylserine (PS) was used. TPA enhanced or reduced the amplitude of the contraction evoked by increased concentrations of K below 39 mmol/L or over 90 mmol/L, respectively, but consistently enhanced the resting tension at any given concentration of high K. Similar effects of TPA were observed on the Ca-induced contraction in saponin skinned muscle tissues. The enhancing action of TPA on the K-induced contraction was not related to activation of either the voltage-dependent Ca channel or the sarcoplasmic reticulum, and did not occur in the case of Ca-independent contraction in skinned muscle tissues. During the enhancement of the contraction induced by TPA, the phosphorylation of myosin light chain and the shortening velocity of contraction as measured using the slack test, were enhanced with no remarkable change in the free Ca concentration in the cytosol. TPA consistently inhibited the ACH-induced contraction accompanied by a marked reduction in free Ca due to inhibition of the hydrolysis of phosphatidyl inositol 4,5-bisphosphate. Under the assumption that TPA possesses the same action as DG, activation of protein kinase C increased the Ca sensitivity of contractile proteins in vascular smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Itoh
T
T
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Fujiwara
T
T
Kubota
Y
Y
Nishiye
E
E
Kuriyama
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D010718:Phosphatidylserines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010718:Phosphatidylserines; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium