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 & 80 micrograms/kg i.c.v.) stimulated antral and duodenal myoelectric activity in 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 duodenal 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. Haloperidol (1 mg/kg i.p.) blocked all the effects of Tyr-MIF-1 whereas sulpiride (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.) antagonized selectively the primary antral stimulation and the initial disruption of duodenal MMC induced by Tyr-MIF-1. L365 260 (10 micrograms/kg i.c.v.) has also antagonized only the initial disruption of duodenal MMCs. DTG and JO 1784 (100 micrograms/kg i.c.v. each) reproduced fully the effect of Tyr-MIF-1 on the duodenum but not that on the antrum. Domperidone, (+)SCH 23390, devazepide, PK 11-195 and flumazenil did not have effect on the action of Tyr-MIF-1. It is concluded that Tyr-MIF-1 stimulates the antrum involving haloperidol sensitive but nondopamine, dopamine, probably sigma receptors, and the duodenum via a pathway where central D2 dopamine, sigma and CCKB receptors are implied.
Million
M
M
Department of Pharmacology, INRA BP3, Toulouse.
Fioramonti
J
J
Bueno
L
L
D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D018492:Dopamine Antagonists; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D004576:Electromyography; D058787:GABA-A Receptor Antagonists; D005769:Gastrointestinal Motility / Q000187:drug effects*; D009075:MSH Release-Inhibiting Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology*
D018492:Dopamine Antagonists; D058787:GABA-A Receptor Antagonists; D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D017480:Receptors, sigma; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone