PMID- 10734153 OWN - NLM STAT- MEDLINE DCOM- 20000421 LR - 20190617 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 293 IP - 1 DP - 2000 Apr TI - Neuromuscular dysfunction in the jejunum and colon of human leukocyte antigen B27 transgenic rats. PG - 60-6 AB - HLA-B27 transgenic rats are a model of spontaneous gastrointestinal inflammation associated with expression of human leukocyte antigen (HLA) B27 and beta(2)-microglobulin. Our goal was to investigate in vitro enteric nerve regulation and contractile activity in isolated longitudinal muscles from the jejunum and colon of HLA-B27 rats. Nontransgenic age-matched Fisher 344 rats were used as controls. Intestinal inflammation and tissue injury, quantified histologically and through tissue myeloperoxidase activity, were evident in both the jejunum and colon of HLA-B27 rats. Although resting tension and spontaneous activity of the jejunal and colonic muscles from HLA-B27 rats did not differ significantly from controls, responses to both enteric nerve stimulation or direct muscle activation were significantly inhibited. In muscles from HLA-B27 rats, electrical field stimulation (0.5 ms, 0.5-20 Hz) induced low-amplitude contractions (maximal reduction 60-65%) compared with respective controls. In the presence of atropine and guanethidine, nonadrenergic and noncholinergic contractile responses to higher frequencies of stimulation (8-20 Hz) were also of lower amplitude. These changes were accompanied by a shift in neurally mediated contractions from predominantly cholinergic in the jejunum and colon of Fisher 344 rats to predominantly nonadrenergic and noncholinergic in HLA-B27 rats. Furthermore, maximal contractions to carbachol or KCl depolarization were reduced (up to 2.7-fold) compared with respective controls. In the jejunum of HLA-B27 rats the EC(50) level for carbachol was decreased. The data indicate that gastrointestinal inflammation induced by expression of HLA-B27 is associated with hypocontractility and inhibition of enteric cholinergic control of the longitudinal muscle in both the small and large intestine. FAU - Venkova, K AU - Venkova K AD - Oklahoma Foundation for Digestive Research Basic Science Laboratories, Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA. FAU - Dunn, S T AU - Dunn ST FAU - Adesina, A M AU - Adesina AM FAU - Greenwood-Van Meerveld, B AU - Greenwood-Van Meerveld B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Adrenergic Agents) RN - 0 (HLA-B27 Antigen) RN - 0 (Muscarinic Agonists) RN - 0 (Muscarinic Antagonists) RN - 660YQ98I10 (Potassium Chloride) RN - 7C0697DR9I (Atropine) RN - 8Y164V895Y (Carbachol) RN - EC 1.11.1.7 (Peroxidase) RN - ZTI6C33Q2Q (Guanethidine) SB - IM MH - Adrenergic Agents/pharmacology MH - Animals MH - Animals, Genetically Modified MH - Atropine/pharmacology MH - Carbachol/pharmacology MH - Colitis/*genetics/*physiopathology MH - Electric Stimulation MH - Enteritis/*genetics/*physiopathology MH - Guanethidine/pharmacology MH - HLA-B27 Antigen/*genetics MH - In Vitro Techniques MH - Jejunal Diseases/*genetics/*physiopathology MH - Male MH - Muscarinic Agonists/pharmacology MH - Muscarinic Antagonists/pharmacology MH - Muscle, Smooth/pathology MH - Neuromuscular Diseases/*genetics MH - Parasympathetic Nervous System/physiopathology MH - Peroxidase/metabolism MH - Potassium Chloride/pharmacology MH - Rats MH - Rats, Inbred F344 EDAT- 2000/03/29 09:00 MHDA- 2000/04/29 09:00 CRDT- 2000/03/29 09:00 PHST- 2000/03/29 09:00 [pubmed] PHST- 2000/04/29 09:00 [medline] PHST- 2000/03/29 09:00 [entrez] PST - ppublish SO - J Pharmacol Exp Ther. 2000 Apr;293(1):60-6.