TACHYKINERGIC NEUROTRANSMISSION IS ENHANCED IN SMALL-INTESTINAL CIRCULAR MUSCLE IN A RABBIT MODEL OF INFLAMMATION

Previous electrophysiological studies have shown that tachykinin-media ted excitatory junction potentials are enhanced in a ricin model of in flammatory bowel disease. The present study extends these findings by investigating the contractile response to stimulation of noncholinergi c nerves and tachykinin agonists. According to rank order potencies, t he rabbit ileal circular muscle was neurokinin (NK)(1) preferring, and the response to these agonists was down-regulated by acetylcholine an d up-regulated by nitric oxide, In ricin-treated tissue, cholinergic a nd nitridergic modulation was lost; in the presence of atropine and N- nitro-L-arginine methyl ester, or tetrodotoxin, the response to NK1 an d NK2 agonists was enhanced. The noncholinergic response to nerve stim ulation was predominantly mediated by NK1 receptors, and the enhanced response of ricin-treated tissue to NK1 agonists probably contributes to the increased response to electrical field stimulation observed und er these conditions. Increased tachykinin response and loss of control of this response by acetylcholine and nitric oxide are likely to have profound effects on intestinal motility and could contribute to some of the symptomology of inflammatory bowel disease.