Neuromuscular dysfunction in the jejunum and colon of human leukocyte antigen B27 transgenic rats.
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.
Venkova
K
K
Oklahoma Foundation for Digestive Research Basic Science Laboratories, Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
Dunn
S T
ST
Adesina
A M
AM
Greenwood-Van Meerveld
B
B
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003092:Colitis / Q000235:genetics* / Q000503:physiopathology*; D004558:Electric Stimulation; D004751:Enteritis / Q000235:genetics* / Q000503:physiopathology*; D006145:Guanethidine / Q000494:pharmacology; D015796:HLA-B27 Antigen / Q000235:genetics*; D066298:In Vitro Techniques; D007579:Jejunal Diseases / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000473:pathology; D009468:Neuromuscular Diseases / Q000235:genetics*; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D009195:Peroxidase / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D018663:Adrenergic Agents; D015796:HLA-B27 Antigen; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011189:Potassium Chloride; D001285:Atropine; D002217:Carbachol; D009195:Peroxidase; D006145:Guanethidine