Fentanyl-related 4-heteroanilido piperidine OHM3295 augments splenic natural killer activity and induces analgesia through opioid receptor pathways.
Recently, the fentanyl-related compound OHM3295 has been shown to induce a naltrexone-sensitive, dose-related analgesia in CD1 mice. However, unlike morphine or fentanyl, which are potent immunosuppressive drugs, OHM3295 has been found to augment splenic natural killer (NK) activity in a dose-related and naltrexone-reversible manner. The present study investigated the type (delta, kappa or mu) of opioid receptor involved in analgesia and immunomodulation after acute administration of OHM3295. CD1 mice pretreated with beta-funaltrexamine (beta-FNA, 40.0 mg/kg) showed an insignificant induction of analgesia (8.4 +/- 3.7%) after 3.2 mg/kg OHM3295, whereas mice pretreated with vehicle, norbinaltorphimine (10.0 mg/kg) or naltrindole (20.0 mg/kg) exhibited 43.6 +/- 12.6% of maximal analgesia, as determined by the tail-flick latency test. Consistent with previous results, acute administration of OHM3295 (3.2 mg/kg) augmented splenic NK activity (20.7 +/- 3.4 lytic units [LU]) relative to vehicle-treated mice (8.2 +/- 0.7 LU). Pretreatment with beta-FNA (40.0 mg/kg) completely blocked (9.0 +/- 1.9 LU) OHM3295-mediated augmentation of NK activity, whereas pretreatment with norbinaltorphimine (10.0 mg/kg) partially blocked (15.8 +/- 2.2 LU) the drug-induced effect. However, pretreatment with naltrindole (20.0 mg/kg) did not antagonize OHM3295-induced increases in splenic NK activity but rather further enhanced (32.3 +/- 4.2 LU) the effect. NK-enriched effector cells from OHM3295-treated mice displayed an increase in conjugation with YAC-1 target cells, an increase in the percent killing of target cells and a significant increase in the number of active killer cells compared with NK-enriched effector cells from vehicle-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Baker
M L
ML
Louisiana State University Neuroscience Center, Louisiana State University Medical Center, New Orleans, USA.
Brockunier
L L
LL
Bagley
J R
JR
France
C P
CP
Carr
D J
DJ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured; D000099192:CD69 Antigens
D000700:Analgesics; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D005283:Fentanyl; D037181:Lectins, C-Type; D017450:Receptors, Opioid, mu; D000099192:CD69 Antigens; C091795:OHM 3295