Regulation of immune functions in rat splenocytes after acute and chronic in vivo treatment with CP-55,940, a synthetic cannabinoid compound.
Changes in mitogen-induced splenocyte proliferation and NK activity were evaluated after acute (1 h) and chronic (6 d) in vivo treatment of rats with the synthetic cannabinoid compound CP-55,940. At a dose of 0.4 mg/kg i.p. it significantly inhibited the splenocyte proliferative response to PHA and NK activity but half this dose (0.2 mg/kg) had no effect on immune responses. Pretreatment of rats with the cannabinoid receptor CB1 antagonist SR141716A did not antagonize the CP-55,940-induced immunosuppression, excluding the activation of this receptor subtype in the mediation of this effect. When immune function studies were done on rats tolerant to CP-55,940-induced analgesia, full tolerance also developed for the inhibition of splenocyte proliferation and NK activity. The data provided indicate that CB1 cannabinoid receptors are not involved in mediating the acute and chronic effects of cannabinoids on the immune system and suggest a possible implication of CB2 receptor although other modalities of CP-55,940 action can not be ruled out.
Patrini
G
G
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy. gori@imiucca.csi.unimi.it
Sacerdote
P
P
Fuzio
D
D
Manfredi
B
B
Parolaro
D
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D003511:Cyclohexanols / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004334:Drug Administration Schedule; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*
D002186:Cannabinoids; C469526:Cnr2 protein, rat; D003511:Cyclohexanols; D007166:Immunosuppressive Agents; D010880:Piperidines; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant