Comparative action of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs on intestinal motility and nociception in rats.
Central (i.c.v.) effects of D-Tyr-D-Leu-[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(1DME)Y8Fa] and D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(3D)Y8Fa], synthetic analogs of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 on intestinal myoelectric activity and nociception were studied and compared to that of D-Ala2-Met5-enkephalinamide in rats. The duration of disruption of intestinal migrating myoelectric complexes, induced by p.o. administration of a test meal was significantly shortened (P < .01) by (1DME)Y8Fa and (3D)Y8Fa (8, 40 and 80 micrograms/kg) and D-Ala2-Met5-enkephalinamide (40 and 80 micrograms/kg). The coadministration of any two of these drugs, at doses of nonmeasurable effect when given alone (2 micrograms/kg), has also reduced the duration (P < .01) of the postprandial intestinal motor profile. Both separate and combined effects of drugs were antagonized by naloxone (1 mg/kg s.c.). In contrast, in the tail-flick test, analgesia induced by D-Ala2-Met5-enkephalinamide (40 micrograms/kg i.c.v.) was blocked by (1DME)Y8Fa, (3D)Y8Fa (8 micrograms/kg) and naloxone (1 mg/kg s.c.). The coadministration of (1DME)Y8Fa and (3D)Y8Fa at doses of no proper effect when given alone (8 micrograms/kg) has significantly (P < .01) reduced the latency time. This effect was not blocked by naloxone (1 mg/kg s.c.). It is concluded that the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs, (1DME)Y8Fa and (3D)Y8Fa, when given i.c.v. exert effects similar to opiate agonists and antagonists on intestinal myoelectrical activity and on nociception, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Million
M
M
Department of Pharmacology and Toxicology, Institut National de la Recherche Agronomique, Toulouse, France.
Fioramonti
J
J
Gicquel
S
S
Zajac
J M
JM
Bueno
L
L
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D009479:Neuropeptides; D009842:Oligopeptides; C062384:tyrosyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C080757:tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide