[Tegaserod inhibits noxious rectal distention induced response and spinal nNOS expression in rats with visceral hypersensitivity].
OBJECTIVE
To examine the effects of 5-HT4 receptor partial agonist tegaserod on response to rectal distention (RD) and on nNOS expression in spinal cord, and to investigate the mechanism of tegaserod influencing visceral sensation.


METHODS
Neonatal SD rats randomLy received colonic irritation by acetic acid from postnatal day 8 to day 21 as visceral hypersensitive model (Group H); or by saline intrarectally as control group (Group C). Five subgroups of Group H were i.p. injected randomLy with saline, vehicle (1-methyl-2-thpyrrolidone) or tegaserod at doses of 0.1, 0.3 and 1.0 mg/kg, respectively. Two subgroups of Group C were i.p. injected with saline or tegaserod at dose of 1.0 mg/kg. Ten minutes after injection rectal distention was performed, AWR was recorded and nNOS expression in spinal cord (L6-S1) was analyzed quantitatively by NADPH-diaphorase histochemistry.


RESULTS
Tegaserod significantly inhibited AWR in Group H, but had no effect in Group C. Tegaserod (1.0 mg/kg) inhibited AWR more significantly in Group H than in Group C at the largest volume of distention (1.2 mL). In Group H, tegaserod (1.0 mg/kg) significantly decreased overall nNOS positive cells in spinal cord to 40% of saline. The greatest attenuation was in dorsal horn (31% of H-saline). Tegaserod (0.1 mg/kg) did not affect the overall nNOS(P>0.20), but decreased the number of nNOS positive cells in central canal (79% of H-saline  P<0.01).


CONCLUSIONS
Tegaserod inhibits response to rectal distention in rats with visceral hypersensitivity and dose  dependently attenuates spinal nNOS expression, especially in dorsal horn and central canal. nNOS may be involved in the modulation of visceral sensitivity by tegaserod.
Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
Hong-mei
HM
Jiao
Peng-yan
PY
Xie
D000818:Animals; D000831:Animals, Newborn; D004108:Dilatation, Pathologic / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D043183:Irritable Bowel Syndrome / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000187:drug effects* / Q000503:physiopathology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology
D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I