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 acti vity, mainly in the central nervous system. The aim of this study was to investigate in rats the role of central neuropeptide FF receptors i n intestinal motor disturbances and body temperature changes induced b y endotoxins and platelet-activating factor (PAF), a major endotoxin m ediator. Rats were fitted with intestinal electrodes, an intraperitone al thermistor probe and an intracerebroventricular (i.c.v.) cannula fo r long-term use. E. coli endotoxin (100 mu g/kg, i.v.) disrupted the c yclic pattern of intestinal migrating myoelectric complexes and induce d a biphasic increase in body temperature while PAF (25 mu g/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 mu g/ kg reduced the duration of migrating myoelectric complex disruption in duced by endotoxin and PAF and abolished the PAF-induced hypothermia. Only at the dose of 100 mu g/kg did (1 DME)Y8Fa change the biphasic en dotoxin-induced hyperthermia into a monophasic increase. Naloxone (I m g/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 change s in body temperature induced by endotoxin and PAF. Its action against endotoxin may involve an anti-opioid pathway whereas its action again st PAF does not. (C) 1997 Elsevier Science B.V.