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Intestinal motor stimulation by the 5‐HT 4 receptor agonist ML10302: differential involvement of tachykininergic pathways in the canine small bowel and colon
Author(s) -
De Ponti F.,
Crema F.,
Moro E.,
Nardelli G.,
Croci T.,
Frigo G. M.
Publication year - 2001
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1365-2982.2001.00295.x
Subject(s) - agonist , medicine , stimulation , tachykinin receptor , cholinergic , endocrinology , receptor antagonist , receptor , atropine , tegaserod , antagonist , pharmacology , chemistry , irritable bowel syndrome , substance p , neuropeptide
5‐Hydroxytryptamine (5‐HT) 4 receptor agonists stimulate gut motility through cholinergic pathways, although there are data suggesting that noncholinergic (tachykininergic) excitatory pathways may also be involved. Differences may exist between the small bowel and colon. Our aims were: (i) to compare the prokinetic effect exerted by the 5‐HT 4 receptor agonist ML10302 in the canine small bowel and colon in vivo; and (ii) to investigate the role of tachykininergic pathways in mediating this response. In fasting, conscious dogs, chronically fitted with electrodes and strain‐gauge force transducers along the small bowel and colon, intravenous injection of ML10302 (35 μg kg –1 ) immediately stimulated spike activity and significantly increased propagated myoelectrical events at both intestinal levels. In the small bowel, the effects of ML10302 were unchanged by previous administration of the selective NK 1 tachykinin receptor antagonist SR140333, the NK 2 tachykinin receptor antagonist SR48968, or the NK 3 tachykinin receptor antagonist SR142801. In the colon, all tachykinin receptor antagonists significantly inhibited stimulation of spike and mechanical activity by ML10302, without affecting ML10302‐induced propagated myoelectrical events. Atropine (100 μg kg –1 i.v.) suppressed the stimulatory effect of ML10302 at both intestinal levels. In conclusion, the 5‐HT 4 receptor agonist ML10302 induced significant prokinesia both in the small bowel and colon through activation of cholinergic pathways. Tachykininergic pathways are not involved in the ML10302‐induced prokinesia in the small bowel, but they play an important role in mediating the colonic motor response to ML10302.