Blockade of lipopolysaccharide-induced fever by a mu-opioid receptor-selective antagonist in rats.
The endogenous opioid system has been found to be involved in fever caused by pyrogens. In the present study, we have investigated the role of the mu-opioid receptor in the brain in fever induced by lipopolysaccharide. Rats were microinjected with 1 microg of the mu-opioid receptor-selective antagonist, cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), into the preoptic anterior hypothalamus. Thirty minutes later, lipopolysaccharide (50 microg/kg) was injected intraperitoneally (i.p.). CTAP reduced by 1 degrees C the fever induced by lipopolysaccharide. However, it did not affect lipopolysaccharide fever when it was given 3 h after lipopolysaccharide injection. These data indicate that mu-opioid receptors within the preoptic anterior hypothalamus mediate the initiation of lipopolysaccharide fever and suggest that the opioid system is involved in the pathogenesis of fever in rats.
Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA.
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K
Benamar
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Xin
E B
EB
Geller
M W
MW
Adler
D000595:Amino Acid Sequence; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013004:Somatostatin; D013997:Time Factors
C529311:CTAP octapeptide; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D017450:Receptors, Opioid, mu; D013004:Somatostatin