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NEUROREGULATION AND MOTILITY

A 5-HT₄ agonist mosapride enhances rectorectal and rectoanal reflexes in guinea pigs

¹Department of Physiology II, and ²First Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan

Submitted 19 February 2003 ; accepted in final form 25 April 2003

The rectal distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations in guinea pigs were generated through the extrinsic sacral excitatory nerve pathway (pelvic nerves) and the intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The aim of the present study was to evaluate whether a prokinetic benzamide, mosapride, enhances the R-R and R-IAS reflexes mediated via 5-HT₄ receptors in the guinea pig. The mechanical activities of the R and IAS were recorded with a balloon connected to a pressure transducer and a strain gauge force transducer in the anesthetized guinea pig with intact spinal-intestinal pathways. Gradual and sustained rectal distension evoked R-R contractions and synchronous R-IAS relaxations. Mosapride (0.1–1.0 mg/kg iv) dose-dependently enhanced both R-R and R-IAS reflex responses. Reflex indexes for R-R and R-IAS maximally increased from 1.0 (control) to 1.92 and 1.88, respectively. A specific 5-HT₄ receptor antagonist, GR 113808 (1.0 mg/kg iv), antagonized the enhancement of the R-R and R-IAS reflexes induced by mosapride 1.0 mg/kg iv. The present results indicate that mosapride enhanced the R-R and R-IAS reflexes mediated through 5-HT₄ receptors.

extrinsic reflex; internal anal sphincter; intrinsic reflex; rectum

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