CNS blockade of acoustic stress-induced gastric motor inhibition by kappa-opiate agonists in dogs.
The influence of the kappa-opioid substances dynorphin-(1-13), ethylketocyclazocine (EKC), and U 50488 and mu-opioid substance [D-Ala2-N-Me, p-nitro-Phe4-Gly5-ol]enkephalin (DAGO) on gastric motor inhibition induced by acoustic stress (AS) was investigated in fasted dogs with strain-gauge transducers chronically implanted on the antrum and proximal jejunum. AS induced by 1 h of music (80-90 dB) was delivered through earphones. Starting 40-50 min after the last migrating motor complex (MMC), AS delayed by 114% the occurrence of the next gastric MMC, whereas intestinal motility was unaffected. During AS plasma cortisol increased (P less than 0.05) by 215%, 15 min after the beginning of noise and reached a peak at 30 min. When administered intracerebroventricularly at doses higher than 20 ng/kg, dynorphin abolished the AS-induced lengthening of the gastric MMC cycle. Similar blockade was observed for EKC and U 50488 at doses of 10 and/or 20 ng/kg, but DAGO was unable to affect the AS-induced gastric inhibition at any dosage tested (20-200 ng/kg icv). At doses effective against AS-induced hypomotility, both dynorphin-(1-13) and EKC reduced significantly (P less than or equal to 0.05) the associated maximal increase in plasma cortisol level. Plasma cortisol was unmodified by intracerebroventricular administration of DAGO. None of the agonists affected basal plasma cortisol levels or the increase (0-90 min) in response to intravenous adrenocorticotropic hormone (ACTH, 5 IU). Both EKC (50 ng/kg) and U 50488 (20 ng/kg) were unable to antagonize the inhibitory effect of ovine corticotropin-releasing factor (CRF, 100 ng/kg icv).(ABSTRACT TRUNCATED AT 250 WORDS)
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000161:Acoustic Stimulation; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004399:Dynorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D016314:Ethylketocyclazocine; D005769:Gastrointestinal Motility / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D011759:Pyrrolidines / Q000494:pharmacology*; D013312:Stress, Physiological / Q000503:physiopathology*
D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D000324:Adrenocorticotropic Hormone; D003496:Cyclazocine; D006854:Hydrocortisone