Hypothalamic opioids and the acute-phase glycoprotein response in guinea pigs.
Endogenous opioids (EO) probably do not modulate endotoxin (LPS)- or interleukin 1 (IL1)-induced fever because naloxone does not prevent its development. Yet, increases in CSF and hypothalamic levels of beta-endorphin have been reported during LPS-and IL1-induced fevers. Since IL1 also reduces the specific binding of opioids to their receptors in guinea pig brain, the opioids could be involved in modulating nonfebrile effects of IL1. To determine whether EO might have a role in the IL1-induced acute-phase glycoprotein response of guinea pigs, (1) naloxone (5 and 10 mg/kg, SC) was injected prior to LPS (S. enteritidis 2 micrograms/kg, IV; N = 5), and (2) morphine (MOR, 10 micrograms/microliter), [D-ala2]-met-enkephalinamide (DAME, 5 micrograms/microliter), or dynorphin A (DYN, 5 micrograms/microliter) was injected into the preoptic area (1 microliter, bilaterally; N = 8/treatment) or into the 3rd ventricle (N = 4/treatment); pyrogen-free saline was the control injection. Measurements were: core temperature (Tco) and, as indices of acute-phase glycoproteins, plasma levels of copper (Cu) and N-acetylneuraminic acid (NANA). Naloxone did not prevent the fever or the increases in plasma Cu and NANA levels evoked by LPS. The intracerebral administration of opioid agonists by either route induced variable rises in Tco, each with a different pattern, but no increases in plasma Cu and NANA levels. Thus, EO do not participate in the central modulation of acute-phase glycoprotein synthesis, but may have a role in influencing other nonthermal IL1 effects in the CNS.
Ahokas
R A
RA
Seydoux
J
J
Llanos-Q
J
J
Mashburn
T A
TA
Blatteis
C M
CM
D000209:Acute-Phase Proteins; D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis*; D004399:Dynorphins / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005334:Fever / Q000209:etiology / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006168:Guinea Pigs; D007031:Hypothalamus / Q000503:physiopathology*; D007375:Interleukin-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D000209:Acute-Phase Proteins; D001798:Blood Proteins; D004723:Endorphins; D006023:Glycoproteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D004399:Dynorphins; D009020:Morphine