Cholinergic modulation of the release of serotonin in the gastric interstitial fluid. An in vivo study in rabbits.

Dialysis fibers chronically implanted into the gastric submucosa of rabbits allowed us to simultaneously (a) collect an interstitial fluid dialysate in which 5-hydroxytryptamine concentrations were measured, and (b) locally perfuse drugs such as acetylcholine, neostigmine, and atropine, which stimulated the release of 5-hydroxytryptamine. The effect of acetylcholine was not blocked by atropine but was blocked by hexamethonium. Furthermore, 5-hydroxytryptamine concentrations in the interstitial fluid were lower when acetylcholine and hexamethonium were injected together than when hexamethonium was injected alone. We conclude that acetylcholine stimulates the release of 5-hydroxytryptamine into the gastric interstitial fluid by acting on nicotinic receptors, and has inhibitory effects by stimulating the muscarinic receptors.

Effect of diet on intestinal xylose absorption in dogs.

The absorption of xylose at different levels of the intestine was compared in five dogs receiving diets containing either wheat bran, polyethylene particles (PE), or horse-bean hulls. The absorption was determined by serial collection of the interstitial fluid (ISF) in different parts of the small intestine and colon, and blood concentration after the administration of D-xylose as a solution (0.5 g/kg body weight) into the duodenal bulb. Xylose was mostly absorbed from the duodenum, and its concentration in the duodenal ISF and in plasma was reduced on a diet containing fiber, irrespective of the nature of fiber. In contrast, a negative linear relation between the mean retention time of digesta in the small intestine and the amount of xylose absorbed by duodenum was evidenced (r = -0.843). The results indicate that changes in transit linked to the presence of fiber in a diet are a major operative factor in the rate of carbohydrate absorption. They suggest that the absorption can be affected by a relatively minor change in the intestinal transit of digesta.

Local release of monoamines in the gastrointestinal tract: an in vivo study in rabbits.

Dialysis fibers chronically implanted into the gastric submucosa of rabbits allowed us to collect an interstitial fluid (I.S.F.) dialysate in which biogenic amine concentrations were measured, and compared with those obtained from plasma and tissue samples. The results suggest that I.S.F. concentrations represent a good assessment of the local release of the amines by enteric nerves and/or paracrine cells, under basal conditions. The fact that acetylcholine and neostigmine, when perfused through the dialysis system, increased I.S.F. serotonin (5-HT) concentrations, supports a cholinergic modulation of the release of 5-HT within the gastrointestinal wall, and validates the dialysis method as a powerful tool to monitor, in vivo, dynamic changes in I.S.F. monoamine concentrations.

Measurement of monoamines and their metabolites in the interstitial fluid of the gut.

Bundles of hollow dialysis fibers were surgically implanted into the submucosa of the stomach and intestine allowing collection of an interstitial fluid (ISF) dialysate. Measurement of monoamines and their metabolites in ISF was performed using high-performance liquid chromatography with electrochemical detection. The local concentration of L-5-hydroxy-tryptophan (5-HTP) in ISF from the antrum was determined in conscious rats after intraperitoneal loading with 5-HTP. The metabolite was similarly evaluated after the administration of levodopa (L-DOPA). Validation of ISF dialysis as a method for determining changes of biogenic amine concentration in the extracellular fluid was determined for the antrum, duodenum, and colon in dogs after the oral or subcutaneous administration of 5-HTP as a precursor of serotonin and 5-hydroxyindole acetyl acetic acid. The proposed procedure provides a novel approach in pharmacologic studies, where a direct correlation between the distribution of a drug and its metabolites (pharmacokinetics) and their effects (pharmacodynamics) has to be measured.