In vivo assessment of the regulatory mechanism of cholinergic neuronal activity associated with motility in dog small intestine.

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. Intra-arterial 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.

Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility.

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.

Acceleration by KW-5092 of intestinal motility associated with acetylcholine release in vivo.

Effect of KW-5092 ([1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2- imidazolidinylidene]propanedinitrile fumarate) on intestinal motility and release of endogenous acetylcholine (ACh) were measured simultaneously in the small intestine of anesthetized dog using the in vivo microdialysis method. Intraarterial and intravenous administrations of KW-5092 accelerated the intestinal motility and increased dialysate ACh concentrations. These KW-5092-induced responses paralleled the increase in blood concentration of KW-5092. Thus, the acceleration of intestinal motility by KW-5092 was found in vivo to be associated with an increase in ACh release from the intestinal cholinergic neurons.

In vivo microdialysis assessment of nerve-stimulated contractions associated with increased acetylcholine release in the dog intestine.

Intestinal contractility and release of endogenous acetylcholine (ACh) were measured simultaneously in vivo in the small intestine of the anesthetized dog. Electrical stimulation of nerves in the intestinal seromuscular layers caused contractions and increased concentrations of ACh in the dialysate, which were abolished by infusion of tetrodotoxin into the intestinal marginal artery at 75 nmol/ml. Intraarterial administration of atropine at 150 nmol/ml abolished the stimulated contractions, without significant effects on increases in concentrations of dialysate ACh. Thus, the nerve-stimulated contractions were found in vivo to be associated with a local increase in ACh release from the intestinal cholinergic neurons.