Biochemical alterations in colonic smooth muscle from cats with idiopathic constipation and megacolon

Mediation of acetylcholine and substance P induced contractions by myosin light chain phosphorylation in feline colonic smooth muscle

“…Muscle strips were suspended in the longitudinal muscle orientation and attached to isometric force transducers d as described. 8,14 Muscle strips were placed under an initial passive load of 100 mg and allowed to equilibrate at this initial muscle length for 45 minutes. Tissues were washed 3 times, approximately 15 minutes apart, during the equilibration period.…”

“…Acquisition and analysis of active isometric force data were performed by use of transducer amplifiers, e signal conditioner, e analog-to-digital converter, e computer software, e and computer f as described. 8,9,12 Chemical stimulation-Muscles were stimulated with bolus or cumulative doses of ACh c (10 -8 to 10 -4 M) or SP c (10 -11 to 10 -7 M), isometric stress responses were recorded, and the agonists were washed out of the muscle baths. To determine the role of calmodulin in ACh-and SP-induced contractions, muscle strips were incubated with N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7, f a calmodulin antagonist 17 ; 100 to 1,000 mM) for 45 minutes, and the muscles were restimulated with ACh or SP.…”

“…[5][6][7] We have previously reported that megacolonic smooth muscle develops less active isometric stress in response to neurotransmitters (eg, acetylcholine [ACh], substance P [SP], and cholecystokinin), membrane depolarization (in response to K + ), and electrical field stimulation. 8,9 Differences in active isometric stress were observed in longitudinal and circular smooth muscle from proximal and distal portions of the colon. Passive isometric stress of megacolonic smooth muscle was unaffected.…”

“…Taken collectively, these data suggest that there is an overall decrease in the contractility of megacolonic smooth muscle independent of agonistreceptor interactions. 8,9 The biochemical basis for these changes was not investigated, but the lesion could involve any element of the signal transduction pathway between agonist-receptor interaction and calcium activation of crossbridge cycling.…”

Idiopathic and secondary acquired megacolon in dogs is associated with diminished vasoactive intestinal polypeptide innervation of the affected colon

“…In particular, it is unknown whether there are abnormalities involving the extrinsic nerves, the enteric nerve plexuses (Gatuso et al, 1998;Iantorno et al, 2007), interstitial cells of Cajal (Lee et al, 2005) or the intestinal smooth muscle (Washabau and Stalis, 1996). Abnormalities of any of these components could lead to gut dilatation and impaired motility (Olsson and Holmgren, 2001).…”