Alpha adrenergic and mu-2 opioid receptors are involved in morphine-induced suppression of splenocyte natural killer activity.
The immunosuppressive effects following acute morphine administration have been mapped to opioid receptors in the central nervous system, specifically to the periaqueductal gray matter of the mesencephalon. The mesencephalon is associated with sympathetic neuronal processes, and the spleen is innervated with sympathetic neurons that are in direct apposition with lymphocytes in the periarteriolar lymphatic sheath. Accordingly, we investigated adrenergic involvement following morphine administration on natural killer (NK) activity by splenic lymphocytes. Acute morphine administration (25 mg/kg s.c.) suppresses (30-50%) NK activity by murine splenic immunocytes as measured in a 4-hr 51Cr-release assay. The suppression is blocked by phentolamine (4 mg/kg) and propranolol (10 mg/kg) in a dose-dependent fashion. However, phentolamine (2 mg/kg), but not propranolol (5 mg/kg), can also effectively antagonize morphine-induced immunosuppression. In addition, phentolamine (4 mg/kg) and prazocin (1 mg/kg), but not yohimbine (1 mg/kg), antagonizes morphine-elicited suppression of splenic NK activity. Selective opioid receptor antagonists were also utilized to determine the type or subtype of receptor activated following morphine administration. beta-Funaltrexamine (40 mg/kg) but not naloxonazine (35 mg/kg), naltrindole (20 mg/kg) or norbinaltorphimine (10 mg/kg) effectively blocks morphine-induced suppression of splenic NK activity. Collectively, morphine interacts with 1) mu-2 opioid receptors (most probably centrally) and 2) activates both alpha and beta adrenergic pathways.
Department of Microbiology, Immunology and Parasitology, Louisiana State University Medical Center, New Orleans.
D J
DJ
Carr
B M
BM
Gebhardt
D
D
Paul
D000818:Animals; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000502:physiology; D013154:Spleen / Q000276:immunology; D001615:beta-Endorphin / Q000097:blood
D007166:Immunosuppressive Agents; D011942:Receptors, Adrenergic, alpha; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; D009020:Morphine