Vol.7, No 1, 2000 pp. 26 -30
UC 615.5
THE IMMUNOMODULATING EFFECTS
OF SPECIFIC OPIOID ANTAGONISTS
Zorica Mančev1, Gordana Pešić1, Stanislava
Stanojević2, Jelena Radulović2
1Departments of Pharmacology and Toxicology, Faculty of
Medicine, University of Niš, Yugoslavia
2Immunology Research Center "Branislav Janković", Belgrade,
Yugoslavia
Summary. The role of central opioid receptor types in the modulation
of humoral immune response was not investigated so far. Therefore, the
aim of the present work was to investigate the possible role of these receptors
in immunomodulation. For this purpose, male Wistar rats were intracerebroventricularly
(icv) injected with opioid receptor specific antagonists. Control groups
of rats were treated icv with physiological saline. Primary humoral immune
response was determined by the "plaque-forming cell assay" (PFC response).
ICI 174864, a selective ? opioid receptor antagonist, administered icv
at doses of 0.1; 1; 10; 20 and 50 ?g/kg bw caused a statistically significant
immunosuppression. ?-funaltrexamine (?-FNA), specific ? opioid receptor
antagonist, applied icv produced a significant immunosuppression only at
lower doses of 0.01 and 0.1 ?g/kg. Nor-binaltorphimine (nor-BNI), a selective
? opioid receptor antagonist administered icv, produced significant immunopotentiation
at all applied doses (0.1; 1; 10 and 50 ?g/kg bw) except for the lowest
dose 0.01 ?g/kg bw. Quaternary naltrexone (QNTx), which is a ? opioid antagonist
at lower doses, but a nonselective opioid antagonist at higher doses, caused
statistically significant potentiation on PFC response only when it was
given icv at doses of 1 and 10 ?g/kg bw. The results indicated differential
involvment of central opioid receptor subtypes in immunomodulation.
Key words. Immunomodulation, PFC response, opioid receptors,
opioid antagonists
IMUNOMODULATORNI EFEKTI SPECIFIČNIH ANTAGONISTA
OPIOIDNIH RECEPTORA POSLE NJIHOVE APLIKACIJE U BOČNE KOMORE MOZGA
Kratak sadržaj: Uloga samostalno intracerebroventrikularno (icv)
primenjenih antagonista opioidnih receptora na humoralni imuni odgovor
do danas nije proučavana. Stoga je cilj ovog rada bio da rasvetli efekte
ovih supstancija u imunomodulaciji. U tu svrhu koristili smo Vistar pacove,
težine 200-250 g, koji su čuvani pod standarnim uslovima. Suptancije su
icv aplikovane i sve grupe imale su kontrolne grupe koje su bile tretirane
ekvimolarnim fiziološkim rastvorom. Imuni odgovor je odredjivan merenjem
broja hemolitičkih plaka (PFC) odgovor. ICI 174864, selektivni delta opioidni
antagonist, icv aplikovan u dozama od 0,1;1;10;20 i 50 ?g/kg tt prouzrokovao
je statistički značajnu imunosupresiju. Beta-funaltreksamin (beta-FNA),
specifični mi opioidni antagonist icv aplikovan izazvao je statistički
značajnu imunosupresiju, kada je bio primenjen u dozama 0,01 i 0,1 ?g/kg
tt. Nor-binaltorfimin (nor-BNI), selektivni kapa opioidni antagonist icv
primenjen, prouzrokovao je statistički značajnu imunopotencijaciju u svim
aplikovanim dozama (0,1; 1; 10 i 50 ?g/kg tt), izuzev u najnižoj dozi (0,01
?g/kg tt). Kvaternerni naltrekson (QNTx) koji se ponaša kao mi opioidni
antagonist u nižim dozama, a delta opioidni antagonist u višim dozama,
ne prelazi krvno moždanu barijeru icv aplikovan izazvao je statistički
značajnu potencijaciju PFC odgovora, ali samo kada je primenjen u dozama
od 1 i 10 ?g/kg tt.
Ključne reči: Imunomodulacija, PFC odgovor, opioidni receptori,
opioidni antagonisti
