ORAL-ADMINISTRATION OF TYR-MIF-1 STIMULATES GASTRIC-EMPTYING AND GASTROINTESTINAL MOTILITY IN RODENTS

The effects of orally administered Tyr-MIF-1, an agonist of an endogenous antiopiate system, were examined on gastric emptying in mice and gastrointestinal myoelectric activity in rats. Tyr-MIF-1 (5 mg/kg in mice, 20 mg/kg in rats) accelerated gastric emptying of a methylcellulose test meal, increased the frequency of antral spike bursts, and disrupted intestinal migrating myoelectric complexes. These effects were reproduced by a subcutaneous administration of Tyr-MIF-1 at the same dosage. They were blocked by naloxone (1 mg/kg) but not by the kappa receptor subtype antagonist MR 2266 (1 mg/kg). The GABA(A) antagonist bicuculline (0.5 mg/kg), but not the GABA(B) antagonist 2-hydroxysaclofen (4 mg/kg), also antagonized the effects of Tyr-MIF-1. These data demonstrate that oral Tyr-MIF-1 stimulates gastric emptying and gastrointestinal motility through a systemic or central action that involves opioid and GABA systems.