Neuromuscular dysfunction in the jejunum and colon of human leukocyte antigen B27 transgenic rats

HLA-B27 transgenic rats are a model of spontaneous gastrointestinal inflamm ation associated with expression of human leukocyte antigen (HLA) B27 and b eta(2)-microglobulin. Our goal was to investigate in vitro enteric nerve re gulation and contractile activity in isolated longitudinal muscles from the jejunum and colon of HLA-B27 rats. Nontransgenic age-matched Fisher 344 ra ts were used as controls. Intestinal inflammation and tissue injury, quanti fied histologically and through tissue myeloperoxidase activity, were evide nt 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 ra ts did not differ significantly from controls, responses to both enteric ne rve stimulation or direct muscle activation were significantly inhibited. I n muscles from HLA-B27 rats, electrical field stimulation (0.5 ms, 0.5-20 H z) induced low-amplitude contractions (maximal reduction 60-65%) compared w ith respective controls. In the presence of atropine and guanethidine, nona drenergic and noncholinergic contractile responses to higher frequencies of stimulation (8-20 Hz) were also of lower amplitude. These changes were acc ompanied by a shift in neurally mediated contractions from predominantly ch olinergic in the jejunum and colon of Fisher 344 rats to predominantly nona drenergic and noncholinergic in HLA-B27 rats. Furthermore, maximal contract ions to carbachol or KCI depolarization were reduced (up to 2.7-fold) compa red with respective controls. In the jejunum of HLA-B27 rats the EC50 level for carbachol was decreased. The data indicate that gastrointestinal infla mmation induced by expression of HLA-B27 is associated with hypocontractili ty and inhibition of enteric cholinergic control of the longitudinal muscle in both the small and large intestine.