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KMID : 0812020080140010024
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Korean Journal of Neurogastroenterology and Motility
2008 Volume.14 No. 1 p.24 ~ p.31
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The Mechanism of 5-Hydroxytryptamine4 (5-HT4) Receptor Partial Agonist (Tegaserod) on Rat Colonic Motility
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Kim Mi-Sung
Park Seon-Mee
Youn Sei-Jin
Chae Hee-Bok
Jeon Won-Joong
Ko Byung-Seong
Oh Seok Jin
Han Joung Ho
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Abstract
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Backgrounds/Aim: A 5-Hydroxytrypatmine4 (5-HT4) partial agonist, Tegaserod (Tega), stimulated the peristaltic reflex in vitro and increases canine intestinal and colonic motility and transit. The objectives of this study were to investigate the action mechanism of Tega on colonic motility using a vascularly perfused rat colon.
Methods: Thirty three Sprague-Dawley rat colons with attached superior mesenteric arteries (SMA) were isolated. Tega was administered to SMA and the intraluminal pressures were monitored in the proximal and distal colon of them. Phentolamine, propranolol, examethonium, atropine (ATR) or tetrodotoxin (TTX), 140 of pM Tega administered and the pressures were monitored.
Results: Contractile responses were increased significantly by Tega at concentrations of 10, 70, 140 and 1400 pM in the proximal colon (40±20.17, 101±92.43, 122±120.57 and 101±89.05%, respectively) and in the distal colon (20±22.05, 73±41.47, 93±75.45 and 73±54.91%, respectively)(p<0.05). In particular, the stimulating effects of Tega on colonic motility were more potent in the proximal colon than in the distal colon. In addition the motility of the distal colon was increased by Tega in a concentration-dependent manner at concentrations of 10, 70 and 140 pM (P<0.05). The effect of Tega was inhibited by ATR but not by other drugs in the proximal and distal colon.
Conclusions: Tega increased colonic motility in vascularly perfused rat colon. The activation of the muscarinic receptor rather than by TTX-senstive nerve conduction might be responsible for the excitatory effect of Tega on colonic motility in rats. (Kor J Neurogastroenterol Motil 2008;14:24-31)
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KEYWORD
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5-Hydroxytryptamine4, 5-HT4, Tegaserod(Tega), Colonicmotility, Cholinergic
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