| Abstract | It is known that 5-HT(4) receptors in the colon of guinea pigs show a distribution similar to that in humans. Thus, we examined the effects of mosapride citrate (mosapride) and cisapride, two 5-HT(4)-receptor agonists, on colonic motility in conscious guinea pigs implanted with force transducers. Mosapride and cisapride administered intragastrically at doses of 3 - 30 mg/kg significantly enhanced the colonic motility. The enhancing effect of mosapride was antagonized by atropine or GR113808, a 5-HT(4)-receptor antagonist, but not by methysergide, a 5-HT(1)- and 5-HT(2)-receptor antagonist; ondansetron, a 5-HT(3)-receptor antagonist; or CP-99994, a tachykinin NK(1)-receptor antagonist. In vitro receptor autoradiography showed that mosapride and cisapride inhibit the specific binding of [(125)I]-SB207710, a selective radioligand of 5-HT(4) receptors, in the colon of guinea pigs. These results suggest that mosapride enhances colonic motility through the 5-HT(4)-receptor activation in guinea pigs and may be useful for treating constipation in patients with colonic motility dysfunction. |
| Authors | Atsuko Inui, Takashi Yoshikawa, Ryuji Nagai, Naoyuki Yoshida, Tsugutaka Ito
(Affiliation: Department of Safety Pharmacology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Suita, Osaka, Japan.)
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| Journal | Japanese journal of pharmacology
(Jpn J Pharmacol)
Vol. 90
Issue 4
Pg. 313-20
(Dec 2002)
ISSN: 0021-5198 Japan |
| PMID | 12501007
(Publication Type: Comparative Study, Journal Article)
|
| Chemical References |
- Benzamides
- Dioxanes
- Morpholines
- Piperidines
- Receptors, Serotonin
- SB 207710
- Serotonin Agonists
- Serotonin Antagonists
- mosapride
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| Topics |
- Animals
- Autoradiography
- Benzamides
(pharmacology)
- Colon
(drug effects, metabolism, physiology)
- Dioxanes
(metabolism)
- Dose-Response Relationship, Drug
- Gastrointestinal Motility
(drug effects)
- Guinea Pigs
- Male
- Morpholines
(pharmacology)
- Piperidines
(metabolism)
- Radioligand Assay
- Receptors, Serotonin
(drug effects, metabolism)
- Serotonin Agonists
(pharmacology)
- Serotonin Antagonists
(pharmacology)
- Time Factors
|
