sincalide and naltrindole

Published results suggest that delta-opioid agonists can modulate the mu-mediated analgesia. In this work, the antinociceptive effects produced by the mu agonist [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin or the mixed inhibitor of enkephalin-degrading enzymes RB 101 (N- [(R,S)-2-benzyl-3[(S)(2-amino-4-methyl- thio)butyldithio]-1-oxopropyl]-L-phenylalanine benzyl ester) were studied after administration of the systemically active and selective delta agonist Tyr-D-Ser(O-tert-butyl)-Gly-Phe-Leu- Thr(O-tert-butyl). In the hot-plate test in mice, Tyr-D-Ser(O-tert-butyl)-Gly- Phe-Leu-Thr(O-tert-butyl) (i.v.) potentiated the antinociceptive responses elicited by [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin (i.v.) or RB 101 (i.v.). These facilitatory effects were reversed not only by prior administration of the delta-selective antagonist naltrindole (0.5 mg/kg s.c.), but also unexpectedly by the selective cholecystokinin CCK-A antagonist MK-329 (20 micrograms/kg i.p.). In addition, the CCK analog [Boc- Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-Phe-NH2] (a mixed CCK-A/CCK-B agonist) increased the jump latency and this effect was blocked by MK-329 (20 micrograms/kg i.p.) and by naloxone, but not by the selective CCK-B antagonist L-365,260 (5 mg/kg i.p.). In contrast, the selective CCK-B agonist BC 264 (62 micrograms/kg i.v.) produced a hyperalgesic effect that was antagonized by L-365,260 (5 mg/kg i.p.). Taken together, these findings suggest that the potentiating effects of delta agonists on mu-mediated analgesia are due to an increase in the release of endogenous CCK interacting with CCK-A and CCK-B receptors and resulting in positive and negative regulation of the endogenous opioid system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Sequence; Analgesia; Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Disulfides; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Male; Mice; Molecular Sequence Data; Naloxone; Naltrexone; Oligopeptides; Peptide Fragments; Phenylalanine; Receptors, Opioid, delta; Receptors, Opioid, mu; Sincalide

Our objective was to study the mechanism of action of cholecystokinin (CCK) on the motility of the gastroduodenal area. Chickens were implanted with five electrodes for electromyography in the stomach and duodenum. The effects of CCK (10(-9) mol.kg-1.10 min-1) were studied against the presence of several antagonists and in vagotomized animals. CCK caused inhibition of gastric motility and duodenal hyperactivity. Vagotomy blocked CCK responses in the stomach but not in the duodenum. Hexamethonium partially blocked gastric inhibition induced by CCK. NG-nitro-L-arginine methyl ester blocked the inhibitory response to CCK in the stomach but did not modify duodenum response. L-Arginine did not modify CCK actions. Opioid antagonists naloxone and naltrindole and adrenergic antagonists phentolamine and propranolol did not modify CCK response. Atropine did not modify duodenal response to CCK. Sodium nitroprusside (10(-8)-10(-6) mol/kg) inhibited gastroduodenal activity in a dose-related manner. We suggest that gastric response to CCK is vagally mediated, mainly by the nitric oxide system. Duodenal hyperactivity seems to be a direct action of CCK. Nitric oxide is a putative neurotransmitter in the chicken gut.

Topics: Animals; Arginine; Atropine; Chickens; Duodenum; Electromyography; Female; Gastrointestinal Motility; Hexamethonium; Hexamethonium Compounds; Male; Membrane Potentials; Muscle, Smooth; Naloxone; Naltrexone; Narcotic Antagonists; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitroprusside; Phentolamine; Propranolol; Sincalide; Stomach; Vagotomy

Topics: Amino Acid Sequence; Analgesics; Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Gastric Emptying; Gastrointestinal Transit; Indoles; Male; Mice; Mice, Inbred ICR; Molecular Sequence Data; Morphinans; Naloxone; Naltrexone; Narcotic Antagonists; Peptide Fragments; Peptides; Phenylurea Compounds; Reaction Time; Receptors, Cholecystokinin; Sincalide