Synchronous phosphorylation of CPI-17 and MYPT1 is essential for inducing Ca(2+) sensitization in intestinal smooth muscle.
Neurogastroenterol Motil
; 23(12): 1111-22, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-22004286
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 Ca(2+) 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 (1µmolL(-1) ) accompanied with muscle contraction. The PKC inhibitor Go6976 (1µmol L(-1) ) inhibited the carbachol-induced phosphorylation of CPI-17, whereas the Rho-associated kinase (ROCK) inhibitor, Y-27632 (10µmol 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 ß-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 Ca(2+) sensitization due to carbachol with GTP. CONCLUSIONS & INFERENCES: In conclusion, receptor stimulation increases the Ca(2+) 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Calcio
/
Proteína Fosfatasa 1
/
Intestinos
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Proteínas Musculares
/
Músculo Liso
Límite:
Animals
Idioma:
En
Revista:
Neurogastroenterol Motil
Asunto de la revista:
GASTROENTEROLOGIA
/
NEUROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido