Role of tachykinin NK2 receptors in normal and altered rectal sensitivity in rats.
Irritable bowel syndrome is characterized by visceral hyperalgesia commonly associated with stress and inflammatory processes. We investigated the role of tachykinin NK2 receptors in the ability of trinitrobenzenesulphonic acid (TNBS) and stress to enhance the sensitivity of the rat rectum to distension using a selective tachykinin NK2 receptor antagonist (MEN 11420). Rats were fitted with electrodes implanted in the striated muscles of the abdomen. Rectal distension (RD) was performed with a balloon inflated by steps of 0.4 ml from 0 to 1.6 ml. Five groups were submitted to RD performed 3 days before and after intrarectal instillation of TNBS. Fifteen minutes before RD, rats were treated with saline or MEN 11420 (5 - 100 microg kg(-1) i.v.). Two other groups, submitted to 2 h restraint or sham stress sessions were randomly treated i.v. with saline or MEN 11420 (10 - 200 microg kg(-1)) prior to RD applied 20 min later. The basal response to RD was characterized by a significant increase in the number of abdominal contractions. This response occurred with a threshold volume of 0.8 ml and was dose-dependently reduced by MEN 11420 (5 - 100 microg kg(-1) i.v.). Rectal inflammation lowered the volume of distension producing abdominal contractions to 0.4 ml (allodynia). This effect was either reduced or suppressed by MEN 11420. A similar allodynia was observed after a stress session and this effect was reduced (49%) or suppressed by MEN 11420 at 200 and 100 microg kg(-1), respectively. Tachykinin NK2 receptors are involved in rectal hypersensitivity associated with inflammation and stress. British Journal of Pharmacology (2000) 129, 193 - 199
Toulouse
M
M
Department of Pharmacology, INRA, France. Menarini Ricerche SpA., Florence, Italy.
Coelho
A M
AM
Fioramonti
J
J
Lecci
A
A
Maggi
C
C
Buéno
L
L
D000818:Animals; D003106:Colon / Q000502:physiology; D003187:Compliance / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D012007:Rectum / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
C107754:MEN 11420; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; D014302:Trinitrobenzenesulfonic Acid