The multiple 5-hydroxytryptamine (5-HT, serotonin) receptor subtypes are distinguished. In this article, we described mainly the 5-HT4 receptor of four subtypes of functional 5-HT receptors, 5-HT1, 5-HT2, 5-HT3, and 5-HT4, recognized in the gastrointestinal tract. In-vivo microdialysis experiments determined that activation of the 5-HT4 receptor stimulated intestinal motor activity associated with a local increase in acetylcholine (ACh) release from the intestinal cholinergic neurons in the whole body of dogs. The 5-HT4 receptor-mediated response of ACh release in the antral, corporal, and fundic strips isolated from guinea pig stomach corresponds to the presence of 5-HT4 receptor in the myenteric plexus. In-vitro receptor autoradiograms of the stomach and colon indicate that the distribution of 5-HT4 receptors in human tissues is similar to that in the guinea pig, although density of 5-HT4 receptors in the myenteric plexus of human tissues is lower than that in guinea pig tissues. The 5-HT4 receptors located in the myenteric plexus may participate in gastrointestinal motility, and thus the 5-HT4 agonists and antagonists may be available for treatment of dysfunction of gastrointestinal motility.

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ABSTRACT-Effect of mosapride, a benzamide, on the motor activity associated with the release of endogenous acetylcholine (ACh) from enteric neurons was examined in the ileum of anesthetized dogs using an in vivo microdialysis method and compared with the effect of 5-hydroxytryptamine (5-HT). Intraarterial administration of 5-HT accelerated intestinal motor activity and increased the concentration of dialysate ACh, and the responses were inhibited by SB204070, a specific 5-HT 4 -receptor antagonist, but were apparently not affected by methiothepin, ketanserin and granisetron. Intraarterial administration of mosapride, a prokinetic benzamide, accelerated intestinal motor activity and the concentration of dialysate ACh increased. The effects of mosapride were antagonized by SB204070. Specific

ABSTRACT-Intestinal motor activity associated with acetylcholine (ACh) release was assessed in the small intestine of anesthetized dogs by simultaneous measurement of motor activity and local ACh concentrations within the intestinal wall with in vivo microdialysis. Basal concentration of ACh measured in the dialysate was 1.12 ± 0.08 pmol/ 15 min (n = 10), a value that remained constant until 3 h after perfusion. Intraarterial infusion of tetrodotoxin reduced dialysate ACh concentration, while the motor activity accelerated at the early phase after infusion of tetrodotoxin and then decreased, thereby suggesting that the motor activity is regulated by not only excitatory cholinergic neurons, but also inhibitory neurons. Intraarterial infusion of atropine increased dialysate ACh concentration but reduced motor activity, thereby indicating that the cholinergic neurons are tonically active and the muscarinic autoreceptors operate to inhibit the ACh release. Intraarterial infusion of norepinephrine reduced, but yohimbine increased both motor activity and dialysate ACh concentration, thereby indicating that the adrenergic neurons regulate the motor activity due to control of cholinergic neuronal activity. This in vivo microdialysis method demonstrated in the whole body of animals that the activity of cholinergic neurons was physiologically regulated by itself and adrenergic neurons.Keywords: In vivo microdialysis, Acetylcholine release, Tetrodotoxin, Atropine, NorepinephrineThe mechanism underlying changes in gastrointestinal motility induced by many substances were evaluated by measuring mechanical activity and neurotransmitter release in the isolated preparations. However, findings obtained by in vitro experiments do not always correspond to those in vivo, and thus it cannot be elucidated whether the responses obtained in the isolated preparations are physiologically and/ or pathophysiologically important in the whole body. Application of microdialysis to gastrointestinal tissue may offer a potential advantage over traditional methods using isolated preparations because it allows for continuous, long-term sampling of interstitial solute concentration within the region of gastrointestinal tissues in which a dialysis probe has been placed. Prostaglandin E 2 in interstitial fluid of dog gastric submucosa (1) and catabolism of neurotensin in interstitial fluid of rat gastric submucosa (2) were measured by the in vivo microdialysis method. These studies did not analyze neuronal regulation of gastrointestinal motility in the whole body, since the concentrations of substances released into the local area related to the motility were not measured. Recently, it has been shown by the in vivo microdialysis method that stimulation of vagal nerve produces release of nitric oxide at concentrations able to cause inhibition of smooth muscle contractions in the stomach and colonic wall of rabbits (3). We previously suggested that the intestinal motility was associated with acetylcholine (ACh) release from enteric nerves in whole body...

Abstract. Characterization of the g-aminobutyric acid (GABA) B receptor involved in the motility of dog small intestine was analyzed by application of the microdialysis method to the small intestine of the whole body of the dog. The reverse transcription-polymerase chain reaction (RT-PCR) was used. Intraarterial administration of muscimol induced acceleration of motility associated with acetylcholine (ACh) release, these responses being antagonized by bicuculline. Intraarterial administration of baclofen induced inhibition of motility associated with ACh release, these responses being antagonized by CGP62349. GABA induced inhibition of motility associated with decrease in ACh release. CGP62349 alone induced acceleration of motility associated with increase in ACh release. RT-PCR revealed the presence of mRNAs for both subunits of GABA B receptor, GABA B1 and GABA B2 , in the dog small intestine, although GABA B1 subunits were 6 isoforms of GABA B1 (GABA B1(a) -GABA B1(g) ), except GABA B1(d) . Thus, the GABA B receptor located at cholinergic neurons as a heterodimer with subunits of GABA B1 and GABA B2 in the dog small intestine operates predominantly relative to the GABA A receptor in physiological motility.