Central and peripheral opioid modulation of gastric relaxation induced by feeding in dogs

Abstract

The influence of i.v. vs. i.c.v. administration of [( D-Ala2, MetPhe4, Gly-ol5]enkephalin (DAMGO) and morphine), kappa U 50488 and ethylketocyclazocine and delta ([D-Pen2, D-Pen5]enkephalin (DPDPE)] opioid agonists on gastric relaxation induced by a standard meal was evaluated in conscious dogs with strain-gauge transducers implanted on the gastric fundus and antrum. Under control conditions, the amplitude of the gastric relaxation in response to feeding was 2.46 +/- 0.23 g. Given i.v. 10 min before feeding, both U 50488 (10 micrograms/kg) and ethylketocyclazocine (10 micrograms/kg) significantly (P less than .01) reduced the amplitude of the gastric relaxation by 57 and 68%, respectively, whereas DAMGO and morphine (10 micrograms/kg i.v.) increased markedly the response to feeding by 67 and 51%, respectively. In contrast, DPDPE had no effect on the gastric relaxation induced by feeding. Previous administration of naloxone (0.3 mg/kg i.v.) or MR 2266 (0.3 mg/kg i.v.) blocked the effect of U 50488 on gastric relaxation with no effect per se on the amplitude of response; naloxone also blocked the increase in gastric relaxation induced by DAMGO. When administered i.c.v. (0.1 microgram/kg) DAMGO induced a significant (P less than .05) increase in the amplitude of gastric relaxation whereas U 50488 and DPDPE (0.1 and 1 microgram/kg i.c.v.) had no effect. The effect of i.c.v. DAMGO on gastric relaxation was unaffected by a previous i.v. administration of SR 58002C (1 mg/kg). Truncal vagotomy blocked the increase in gastric relaxation induced by DAMGO (10 micrograms/kg i.v.), but did not change the effect of U 50488 (10 micrograms/kg i.v.) on gastric relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)