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 NK1receptors, 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.
Footnotes
-
Send reprint requests to: Dr. Jon M. Goldhill, Synthelabo Recherche, 10 Rue des Carrieres, 92505 Rueil-Malmaison, France.
-
↵1 This work was funded by grants to T. Shea Donohue (G183EP).
- Abbreviations:
- CL
- confidence interval
- NK
- neurokinin
- L-NAME
- N-nitro-l-arginine methyl ester
- IBD
- inflammatory bowel disease
- SP
- substance P
- EFS
- electric field stimulation
- EJP
- excitatory junction potential
- KBS
- Krebs-bicarbonate-saline
- PPT
- preprotachykinin
- [SAR]SP
- [Sar9,Met11(O2)]substance P
- β-Ala[NKA]
- [β-Ala8]neurokinin A
- L-NAME
- N-nitro-l-arginine methyl ester
- Received September 6, 1996.
- Accepted May 14, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|