devazepide and atosiban

The aim of this study was to localize oxytocin receptor (OTR) in the stomach and to investigate the effect of OT on gastric motility in rats. Western blot and immunohistochemistry methods were used to localize OTR in stomach. The motility of stomach was recorded in vivo (recording of the intragastric pressure), in vitro (recording of the contraction of muscle strips) and on isolated smooth muscle cells. OTR was expressed on cells of both circular and longitudinal muscle of stomach. Systemic administration of OT induced an early transient decrease and a subsequent increase on intragastric pressure. Devazepide (1 mg kg(-1), i.v.), a cholecystokinin-1 (CCK(1)) receptor antagonist, completely abolished the transient response but did not influence the subsequent one. OT (10(-9)-10(-6) mol L(-1)) dose-dependently increased the contraction of the muscle strips of gastric body, antrum, and pyloric sphincter, and decreased the average cell length of isolated smooth muscle cells. Tetrodotoxin and atropine did not influence the effect of OT on muscle strips. Pretreatment with atosiban, an OTR antagonist, inhibited the spontaneous contraction of muscle strips and abolished the excitatory effect of OT on the muscle strips and the isolated cells. These results suggest that the OTR is expressed on the smooth muscle of the stomach and mediates excitatory effect of OT on gastric motility.

Topics: Animals; Blotting, Western; Devazepide; Gastric Mucosa; Gastrointestinal Motility; Hormone Antagonists; Immunohistochemistry; Male; Muscle Contraction; Muscle, Smooth; Organ Culture Techniques; Oxytocin; Rats; Rats, Wistar; Receptors, Oxytocin; Stomach; Vasotocin

The effects of oxytocin on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in ovariectomized rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2 51CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of oxytocin (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK1 receptor antagonists, devazepide and lorglumide, effectively attenuated the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK2 receptor antagonist, did not alter the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that oxytocin inhibits gastric emptying and gastrointestinal transit in ovariectomized rats via a mechanism involving the stimulation of CCK release and CCK1 receptor activation.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Female; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Transit; Ovariectomy; Oxytocin; Phenylurea Compounds; Proglumide; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Receptors, Oxytocin; Sincalide; Vasotocin

The effects of oxytocin (OT) on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in female rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)(51)CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of OT (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT- induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the OT-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK(2) receptor antagonist, did not alter the OT-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that OT inhibits gastric emptying and gastrointestinal transit in female rats via a mechanism involving CCK stimulation and CCK(1) receptor activation.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Female; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Transit; Hormone Antagonists; Oxytocin; Phenylurea Compounds; Proglumide; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Vasotocin

The effects of oxytocin (OT) on gastric emptying and plasma levels of cholecystokinin (CCK) were studied in male rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2(51)CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Blood samples were collected for OT and CCK radioimmunoassay. After administration of OT (0.2-0.8 mg x kg(-1)), gastric emptying was inhibited, whereas plasma concentrations of OT and CCK were increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. However, administration of atosiban alone had no effect on gastric emptying. Devazepide (3 mg x kg(-1)), a selective CCKA receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. L-365, 260, a selective CCKB receptor antagonist, did not alter the OT-induced inhibition of gastric emptying. These results suggest that OT inhibits gastric emptying in male rats via a mechanism involving CCK stimulation and CCKA receptor activation.

Topics: Animals; Benzodiazepinones; Devazepide; Gastric Emptying; Hormone Antagonists; Male; Osmolar Concentration; Oxytocin; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Vasotocin