title: A minor role for Ca2+ sensitization in sustained contraction through activation of muscarinic receptor in circular muscle of rat distal colon.
abstract: We previously demonstrated that Ca(2+) sensitization has an essential role for carbachol-induced contraction in the longitudinal muscle of the rat distal colon. In the present study, we extended these studies to clarify the role of Ca(2+) sensitization in contraction induced by the activation of muscarinic receptors in the circular muscle of the rat distal colon. Carbachol induced a rapid phasic contraction followed by a sustained contraction that was significantly lower than the phasic and was superimposed with the rhythmic contractions. The extent of increase in intracellular Ca(2+) concentration that was measured simultaneously with tension recording was dissociated from the phasic contraction, whereas it exhibited to a similar extent as sustained contraction. In alpha-toxin-permeabilized preparations, Ca(2+) induced contraction comprising a rapid phasic and a subsequent low sustained component. After Ca(2+)-induced sustained contraction reached a constant level, guanosine triphosphate (GTP) addition resulted in the enhancement of contractile force in a concentration-dependent manner. Carbachol in the presence of GTP caused a further minimal increase in tension (Ca(2+) sensitization). Chelerythrine, a protein kinase C (PKC) inhibitor, inhibited carbachol-induced Ca(2+) sensitization but not GTP-induced Ca(2+) sensitization. In contrast, Y-27632, a Rho kinase inhibitor, inhibited GTP-induced Ca(2+) sensitization but not that induced by carbachol. Phorbol 12,13-dibutyrate, a PKC activator, increased the sustained contraction. These results suggest that the activation of muscarinic receptor with carbachol induces Ca(2+) sensitization via activation of PKC, but this action is minor in the circular muscle of the rat distal colon as a result of limited coupling between muscarinic receptors and Ca(2+) sensitization via the PKC pathway.
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. takeuchi@vet.osakafu-u.ac.jp
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakajima
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Hata
authors.forename: Yasu-Taka
authors.initials: YT
authors.lastname: Azuma
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009125:Muscle Relaxants, Central; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D000470:Alkaloids; D000577:Amides; D053119:Benzophenanthridines; D002273:Carcinogens; D018679:Cholinergic Agonists; D009125:Muscle Relaxants, Central; D011725:Pyridines; D011976:Receptors, Muscarinic; C108830:Y 27632; D015240:Phorbol 12,13-Dibutyrate; D006160:Guanosine Triphosphate; D002217:Carbachol; C016299:chelerythrine; D002118:Calcium