抄録
A Rho-kinase (ROK)-mediated Ca2+ sensitization of vascular smooth muscle (VSM) contraction plays a critical role in vasospasm. We previously identified sphingosylphosphorylcholine (SPC) as the upstream mediator for the ROK-mediated Ca2+ sensitization of VSM contraction. Although the membrane receptors for SPC were reported as the [Ca2+]i-elevating G-protein-coupled receptors (GPCRs), SPC-induced contractions of intact VSM was not accompanied with any elevation of [Ca2+]i and SPC induced contraction of membrane-permeabilized VSM in the absence of cytosolic GTP which is required for the activation of G-proteins and thus of GPCRs. These findings are compatible with the interaction of SPC with the other membrane components than GPCRs or the direct interaction between SPC and lipid membrane, which may in turn affects the functions of membrane signaling molecules. In addition, we observed the strong link between the SPC-induced contraction and the tissue and cellular cholesterol in VSM, suggesting the possible roles of cholesterol-enriched membrane microdomains, membrane lipid rafts, in the SPC/ROK-induced Ca2+-sensitization of VSM contraction. Thus, we investigated the direct interaction of SPC with model membranes. The measurements of surface plasmon resonance using BIACORE system revealed that SPC highly associates with the model membrane microdomains, lipid rafts and that cholesterol in the model membrane enhances the incorporation of SPC into the membrane. [Jpn J Physiol 55 Suppl:S73 (2005)]
