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

J Pharmacol Exp Ther. 2000 Apr;293(1):60-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / pharmacology
  • Animals
  • Animals, Genetically Modified
  • Atropine / pharmacology
  • Carbachol / pharmacology
  • Colitis / genetics*
  • Colitis / physiopathology*
  • Electric Stimulation
  • Enteritis / genetics*
  • Enteritis / physiopathology*
  • Guanethidine / pharmacology
  • HLA-B27 Antigen / genetics*
  • In Vitro Techniques
  • Jejunal Diseases / genetics*
  • Jejunal Diseases / physiopathology*
  • Male
  • Muscarinic Agonists / pharmacology
  • Muscarinic Antagonists / pharmacology
  • Muscle, Smooth / pathology
  • Neuromuscular Diseases / genetics*
  • Parasympathetic Nervous System / physiopathology
  • Peroxidase / metabolism
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Inbred F344


  • Adrenergic Agents
  • HLA-B27 Antigen
  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Potassium Chloride
  • Atropine
  • Carbachol
  • Peroxidase
  • Guanethidine