Authors studied the regulatory mechanism of protein kinase C on the action of acetylcholine in rabbit carotid artery. The arterial rings were myographied isometrically in an isolated organ bath.
In this study, acetylcholine relaxed phenylephrine-induced contraction of rabbit carotid artery in the presence of endothelium. In the pretreatment of methylene blue or nitro-L-arginine, the action of acetylchioline was reduced. Pretreatment of
phorbol
12-myristate 13-acetate (PMA) attenuated the action of acetylcholine. but PMA did not attenuated it in the presence of staurosporine, suggesting that protein kinase C suppressed the action of acetylcholine. The potency of phorbol ester on the
action of
acetylcholine was PMA>phorbol 12, 13-dibutyrate (PDBu)>phorbol 12, 13-diacetate (PDA), but the direct effect of phorbol on the contraction of arterial rings was PDBu>PMA?PDA. This implied that protein kinase C involved in the contraction of
smooth
muscle and the attenuation of the action of acetylcholine were diffferent. PMA did not affect on A23187-and sodium nitroprusside-induced vasorelaxation. Acetylcholine increased tissue cGMP contents, wlrich was reduced by PMA.
These results suggest that in rabbit carotid artery protein kinase C reduce acetylcholine-stimuated endothelium derived relaxing factor (EDRF) release by affecting membrane receptor, and do not affect on the function of EDRF and cGMP production
in
the
smooth muscle.
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