Mechanism of reduced colonic contractility in experimental colitis: role of sarcoplasmic reticulum pump isoform-2.
Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are inflammatory disorders associated with decreased colonic contractility. Here we show that, in experimental colitis in rat induced by trinitrobenzenesulfonic acid, there is a decrease in contraction in response to carbamoylcholine and the sarco/endoplasmic reticulum Ca(+2) (SERCA) pump inhibitor thapsigargin. However, the decrease in contractility may occur due to decrease in the SERCA pump levels or their inactivation. Therefore, we examined the protein and mRNA levels for SERCA2 isoform, which is predominant isoform in colonic smooth muscle. There was a decrease in the levels of SERCA2 protein and mRNA levels in inflamed colonic muscle. These findings suggest that decreased SERCA pump levels is responsible for a decrease in the Ca(+2) stores in the sarco/endoplasmic reticulum that causes a decrease in the contractility in colonic smooth muscle leading to poor bowel movements.
Al-Jarallah
Aisha
A
Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24923, Jabrya, Safat, 13110, Kuwait.
Oriowo
Mabayoje A
MA
Khan
Islam
I
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid
C506948:Atp2a2 protein, rat; D007527:Isoenzymes; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid; D002217:Carbachol; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases