Effects of neuropeptide FF on intestinal motility and temperature changes induced by endotoxin and platelet-activating factor.
Several effects of bacterial endotoxins involve an opioid pathway and neuropeptide FF is an endogenous peptide known to modulate opioid activity, mainly in the central nervous system. The aim of this study was to investigate in rats the role of central neuropeptide FF receptors in intestinal motor disturbances and body temperature changes induced by endotoxins and platelet-activating factor (PAF), a major endotoxin mediator. Rats were fitted with intestinal electrodes, an intraperitoneal thermistor probe and an intracerebroventricular (i.c.v.) cannula for long-term use. E. coli endotoxin (100 microg/kg, i.v.) disrupted the cyclic pattern of intestinal migrating myoelectric complexes and induced a biphasic increase in body temperature while PAF (25 microg/kg, i.p.) disrupted the migrating myoelectric complexes and induced hypothermia for about 2 h. The neuropeptide FF analog, (1 DME)Y8Fa (D-Tyr-D-Leu[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2) administered i.c.v. 40 and 100 microg/kg reduced the duration of migrating myoelectric complex disruption induced by endotoxin and PAF and abolished the PAF-induced hypothermia. Only at the dose of 100 microg/kg did (1 DME)Y8Fa change the biphasic endotoxin-induced hyperthermia into a monophasic increase. Naloxone (1 mg/kg, s.c.) reduced only the duration of migrating myoelectric complex disruption induced by endotoxin. These results indicate that central neuropeptide FF modulates the intestinal motor disturbances and changes in body temperature induced by endotoxin and PAF. Its action against endotoxin may involve an anti-opioid pathway whereas its action against PAF does not.
Million
M
M
Department of Pharmacology and Toxicology, INRA, Toulouse, France.
Fioramonti
J
J
Zajac
J M
JM
Buéno
L
L
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D016065:Myoelectric Complex, Migrating; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D010972:Platelet Activating Factor; C080757:tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D009270:Naloxone; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide