Persistent and selective effects of inflammation on smooth muscle cell contractility in rat colitis.
Intestinal inflammation affects smooth muscle contractility contributing to altered motility, but changes to the individual smooth muscle cells are not well described. We used video microscopy to study the contractility of circular smooth muscle cells (CSMC) isolated from the rat mid-descending colon throughout the course of TNBS-induced colitis, measuring their shortening response to carbachol (CCh), 5-HT, histamine or high K(+). In control CSMC, CCh caused a maximal shortening response of 28 (2%), similar to that for 5-HT of 27 (1%), but by day 4 of colitis, these responses were decreased by 35% and 37%, respectively. By day 36, all aspects of cholinergic contraction returned to control levels, while 5-HT-induced contraction remained significantly attenuated. In contrast, the contractile responses to histamine remained similar at all time points. K(+)-induced contraction was impaired only on day 4, and the maximal response remained substantially greater than CCh or 5-HT. Colitis caused a 121% increase in CSMC length by day 2 that persisted through day 36, independent evidence for phenotypic change. We conclude that impaired CSMC contractility at both the receptor and non-receptor levels contribute to altered smooth muscle function during colitis. Persistent changes in contractile response remained detectable after resolution of inflammation, and similar events may occur in post-enteritis syndromes seen in humans.
Wells
R W
RW
Gastrointestinal Diseases Research Unit, Queen's University, K7L 5G2, Kingston, Ontario, Canada.
Blennerhassett
M G
MG
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D018715:Microscopy, Video; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
D018679:Cholinergic Agonists; D012701:Serotonin; D006632:Histamine; D014302:Trinitrobenzenesulfonic Acid; D002217:Carbachol; D011188:Potassium