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- Title
Mechanisms involved in carbachol-induced Ca<sup>2+</sup> sensitization of contractile elements in rat proximal and distal colon.
- Authors
Takeuchi, Tadayoshi; Kushida, Masahiko; Hirayama, Nobue; Kitayama, Muneyoshi; Fujita, Akikazu; Hata, Fumiaki
- Abstract
1: Mechanisms involved in Ca2+ sensitization of contractile elements induced by the activation of muscarinic receptors in membrane-permeabilized preparations of the rat proximal and distal colon were studied. 2: In a-toxin-permeabilized preparations from the rat proximal and distal colon, Ca2+ induced a rapid phasic and subsequent tonic component. After Ca2+-induced contraction reached a plateau, guanosine 5'-triphosphate (GTP) and carbachol (CCh) in the presence of GTP further contracted preparations of both the proximal and distal colon (Ca2+ sensitization). 3: Y-27632, a rho-kinase inhibitor, inhibited GTP plus CCh-induced Ca2+ sensitization more significantly in the proximal colon than in the distal colon. Y-27632 at 10?µM had no effect on Ca2+-induced contraction or slightly inhibited phorbol-12,13-dibutyrate-induced Ca2+ sensitization in either proximal or distal colon. Chelerythrine, a protein kinase C inhibitor, inhibited GTP plus CCh-induced Ca2+ sensitization in the distal colon, but not in the proximal colon. The component of Ca2+ sensitization that persisted after the chelerythrine treatment was completely inhibited by Y-27632. 4: In ß-escin-permeabilized preparations of the proximal colon, C3 exoenzyme completely inhibited GTP plus CCh-induced Ca2+ sensitization, but PKC(19-31) did not. In the distal colon, C3 exoenzyme abolished GTP-induced Ca2+ sensitization. It inhibited CCh-induced sensitization by 50 % and the remaining component was inhibited by PKC(19-31). 5: These results suggest that both protein kinase C and rho pathways in parallel mediate the Ca2+ sensitization coupled to activation of muscarinic receptors in the rat distal colon, whereas the rho pathway alone mediates this action in the proximal colon.British Journal of Pharmacology (2004) 142, 657-666. doi:10.1038/sj.bjp.0705820
- Subjects
COLON (Anatomy); CALCIUM in the body; MUSCARINIC receptors; GUANOSINE triphosphate; PROTEIN kinase C; INTESTINES
- Publication
British Journal of Pharmacology, 2004, Vol 142, Issue 4, p657
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705820