کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5828651 | 1558973 | 2013 | 7 صفحه PDF | دانلود رایگان |
Since the introduction of 2-aminoethoxydiphenylborate (2-APB) as a membrane permeable modulator of inositol (1,4,5)-trisphosphate receptors, subsequent studies have revealed additional actions of this chemical on multiple Ca2+-permeable ionic channels in the plasma membrane. However, no reports have yet examined 2-APB as a modulator targeting contractile machinery in smooth muscle, independent of Ca2+ mobilization, namely Ca2+ sensitization. Here, we assessed whether or not 2-APB affects intracellular signaling pathways of Ca2+ sensitization for contraction using α-toxin permeabilized human detrusor smooth muscle. Although contractions were induced by application of Ca2+-containing bath solutions, 2-APB had little effect on contractions induced by 1 µM Ca2+ alone but significantly reversed the carbachol-induced augmentation of Ca2+-induced contraction in the presence of guanosine triphosphate (carbachol-induced Ca2+ sensitization). The rho kinase inhibitor Y-27632 and protein kinase C inhibitor GF-109203X also reversed the carbachol-mediated Ca2+ sensitization. Additional application of 2-APB caused a small but significant further attenuation of the contraction in the presence of GF-109203X but not in the presence of Y-27632. Like carbachol, the rho kinase activator; sphingosylphosphorylcholine, protein kinase C activator; phorbol 12,13 dibutyrate, and myosin light chain phosphatase inhibitor; calyculin-A all induced Ca2+ sensitization. However, the inhibitory activity of 2-APB was limited with sphingosylphosphorylcholine-induced Ca2+ sensitization. This study revealed a novel inhibitory effect of 2-APB on smooth muscle contractility through inhibition of the rho kinase pathway.
Journal: European Journal of Pharmacology - Volume 708, Issues 1â3, 15 May 2013, Pages 14-20