title: Tachykinergic neurotransmission is enhanced in small intestinal circular muscle in a rabbit model of inflammation.
abstract: Previous electrophysiological studies have shown that tachykinin-mediated excitatory junction potentials are enhanced in a ricin model of inflammatory bowel disease. The present study extends these findings by investigating the contractile response to stimulation of noncholinergic nerves and tachykinin agonists. According to rank order potencies, the rabbit ileal circular muscle was neurokinin (NK)1 preferring, and the response to these agonists was down-regulated by acetylcholine and up-regulated by nitric oxide. In ricin-treated tissue, cholinergic and nitridergic modulation was lost; in the presence of atropine and N-nitro-L-arginine methyl ester, or tetrodotoxin, the response to NK1 and NK2 agonists was enhanced. The noncholinergic response to nerve stimulation 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 under 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.
authors.affiliation: Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Goldhill
authors.forename: T
authors.initials: T
authors.lastname: Shea-Donohue
authors.forename: N
authors.initials: N
authors.lastname: Ali
authors.forename: V M
authors.initials: VM
authors.lastname: Piñeiro-Carrero
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007079:Ileitis / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D012276:Ricin / Q000494:pharmacology; D009435:Synaptic Transmission; D015320:Tachykinins / Q000494:pharmacology*
chemical_list: D015320:Tachykinins; D012276:Ricin; D000109:Acetylcholine