CENTRAL ADMINISTRATION OF TYR-MIF-1 STIMULATES GASTROINTESTINAL MOTILITY IN RATS - EVIDENCE FOR THE INVOLVEMENT OF DOPAMINE, SIGMA AND CCK RECEPTORS

The effect of central administration of the endogenous peptide Tyr-MIF -1 (Tyr-Pro-Leu-Gly-NH2) on the gastrointestinal myoelectric activity and its mechanism of action were studied in rats. Tyr-MIF-1 (40 and 80 mu g/kg i.c.v.) stimulated antral and duodenal myoelectric activity i n a multiphasic manner. On the antrum it induced a primary increase of the frequency of antral spike bursts followed by a consecutive return to control value and a second rise of the frequency. Likewise duodena l migrating myoelectric complexes (MMCs) were initially disrupted and replaced by an irregular spiking activity followed by a reaparition of the phase III of the MMCs with increased amplitude and frequency. Hal operidol (1 mg/kg i.p.) blocked all the effects of Tyr-MIF-1 whereas s ulpiride (5 mg/kg s.c.) blocked only the duodenal stimulation without affecting that on the antrum. Similarly BMY-14802 (0.5 mg/kg s.c.) ant agonized selectively the primary antral stimulation and the initial di sruption of duodenal MMC induced by Tyr-MIF-1. L365 260 (10 mu g/kg i. c,v.) has also antagonized only the initial disruption of duodenal MMC s. DTG and JO 1784 (100 mu g/kg i.c.v. each) reproduced fully the effe ct of Tyr-MIF-1 on the duodenum but not that on the antrum. Domperidon e, (+)SCH 23390, devazepide, PK 11-195 and flumazenil did not have eff ect on the action of Tyr-MIF-1. It is concluded that Tyr-MIF-1 stimula tes the antrum involving haloperidol sensitive but non-dopamine, proba bly sigma receptors, and the duodenum via a pathway where central D-2 dopamine, sigma and CCKB receptors are implied.