期刊
NEUROGASTROENTEROLOGY AND MOTILITY
卷 23, 期 12, 页码 1111-E542出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2982.2011.01799.x
关键词
Ca2+ sensitization; CPI-17; ileal smooth muscle; myosin phosphatase; MYPT1
资金
- Ministry of Education, Japan
- Yakult Bio-Science Foundation
- Grants-in-Aid for Scientific Research [20228005, 22658089, 21380178, 22500364] Funding Source: KAKEN
Background Myosin phosphatase activity is regulated by mechanisms involving the phosphorylation of CPI-17 and MYPT1, primarily based on studies with tonic-type vascular smooth muscles. This study examined how these mechanisms contribute to the regulation of contraction of a phasic-type intestinal smooth muscle. Methods Phosphorylation levels, tension, and Ca2+ sensitization was detected in rat ileal smooth muscle. Key Results In rat ileal smooth muscle, phosphorylation level of CPI-17 at Thr(38) and MYPT1 at Thr(853), but not MYPT1 at Thr(696), were increased with carbachol (1 mu mol L-1) accompanied with muscle contraction. The PKC inhibitor Go6976 (1 mu mol L-1) inhibited the carbachol-induced phosphorylation of CPI-17, whereas the Rho-associated kinase (ROCK) inhibitor, Y-27632 (10 mu mol L-1) inhibited the carbachol-induced phosphorylation of both CPI-17 and MYPT1. Application of Go6976 or Y-27632 alone inhibited the carbachol-induced contraction; however, the combined application of these inhibitors did not inhibit the contraction in an additive manner. In beta-escin-permeabilized ileal strip, treatment with antiphosphorylated antibodies for CPI-17 at Thr(38) and MYPT1 at Thr(853) and Thr(696) alone almost completely abolished the Ca2+ sensitization due to carbachol with GTP. Conclusions & Inferences In conclusion, receptor stimulation increases the Ca2+ sensitivity of contractile elements through CPI-17 phosphorylation via the PKC/ROCK pathways and MYPT1 phosphorylation via the ROCK pathway, when these mechanisms operate cooperatively and/or synchronously in intestinal smooth muscle.
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