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The role of phosphodiesterase (PDE) isoforms in regulation of transepithelial Cl secretion was investigated using cultured monolayers of T84 cells grown on membrane filters. Identification of the major PDE isoforms present in these cells was determined using ion exchange chromatography in combination with biochemical assays for cGMP and cAMP hydrolysis. The(More)
Antral electrical arrhythmias were investigated in 32 unanesthetized chronic dog preparations implanted with serosal electrodes and transducers. Five of these animals underwent surgical removal of the duodenal cap and the adjacent hypomuscular segment. In the intact dogs two distinct types of arrhythmias of the basic electric rhythm (BER) were observed.(More)
Drugs that enhance gastrointestinal motility include the benzamide drugs metoclopramide, cisapride and renzapride (BRL-24924). Because these agents also are serotonin-3 (5-HT3) receptor antagonists, which can promote gastric emptying in some species, the motor-stimulating properties of benzamide agents may be due to this mechanism. Metoclopramide (0.3-3.0(More)
Large numbers of polymorphonuclear leukocytes which generate reactive oxygen metabolites are found in mucosa and submucosa of the intestinal wall of subjects suffering from inflammatory bowel disease. We have, therefore, examined the relative influences of hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and N-chloramines such as NH2Cl, on the neurally(More)
The relationship of the surface properties of a group of anionic surfactants to their effects on intestinal water transport was studied. Dose-response inhibition of water transport in everted hamster jejunal segments was obtained with two long chain detergents (sodium dodecyl sulfate and dioctyl sodium sulfocuccinate), a fatty acid (ricinoleate), and(More)
SC-49518 (N-[exo-(hexahydro-1H-pyrrolizine-1-yl)methyl]-2-methoxy-4- amino-5-chlorobenzamide HCl), a new benzamide gastrointestinal prokinetic compound, was investigated to determine its ability to stimulate gastrointestinal motility in vivo and whether these actions could be mediated by agonist activity at the putative 5-hydroxytryptamine (5-HT)4 receptor.(More)
Changes in mechanical events and intracellular levels of cAMP induced by the activation of the 5-HT4 receptor were investigated in the rat esophagus tunica muscularis mucosae preparation. Serotonin (5-HT) and 5 methoxytryptamine (5-MOT; 5-HT4 agonist) caused concentration-related relaxation responses, while 5-carboxamidotryptamine (5-CT; 5-HT1 agonist),(More)
Five Long-Evans hooded rats were trained to lever press according to fixed-ratio 5 reinforcement schedules for 0.06 ml dipper deliveries of 8% w/v ethanol during daily (M-F) 0.5-h experimental sessions. After ethanol self-administration was established, doses of the serotonin 5-HT3 antagonists, ondansetron (0.03-3.0 mg/kg), granisetron (0.01-1.0 mg/kg), and(More)