Thromboxane A2 receptor-mediated tonic contraction is attributed to an activation of phosphatidylcholine-specific phospholipase C in rabbit aortic smooth muscles |
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Authors: | Nakahata N Takano H Ohizumi Y |
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Institution: | Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Sendai, Japan. |
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Abstract: | Thromboxane A2 (TXA2) analogue STA2 produced a tonic contraction in rabbit aortic smooth muscles. In the present study, we examined phosphatidylcholine (PC) hydrolysis as a signaling pathway for the tonic contraction in rabbit aortic smooth muscles. In the primary cultured cells labeled with 3H]choline, STA2 caused an accumulation of 3H]phosphorylcholine, a metabolite of PC by PC-specific PLC, in a concentration-dependent manner. The accumulation of 3H]phosphorylcholine was inhibited by SQ29548, a TXA2 receptor antagonist. In the muscle strips, STA2-induced tonic contraction was potently inhibited by D609, an inhibitor of PC-specific phospholipase C in a concentration-dependent manner with the IC50 of about 10 microM. Norepinephrine-induced tonic contraction was also inhibited by D609 with a weaker potency. These results strongly suggest that stimulation of TXA2 receptor results in the activation of PC-specific phospholipase C to yield diacylglycerol that contributes to the tonic contraction. |
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