![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
DO Freier and BA Fuchs
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Morphine is a drug of abuse with an ability to down-regulate immune responsiveness that could have potentially serious consequences in both heroin addicts and in the clinical environment. The exact mechanism of action by which morphine induces immunosuppression has yet to be clearly determined. A direct mechanism of action is suggested to operate through lymphocyte opiate receptors, but the nature of such receptors is still in question. The alternative, an indirect mechanism of action is proposed to be mediated by two possible pathways, hypothalamic-pituitary-adrenal axis activation with increased production of adrenal corticosteroids, or activation of the sympathetic nervous system and concomitant catecholamine release. Natural killer (NK) cell activity was used to determine potential indirect mechanisms of action for morphine. NK activity in the B6C3F1 mouse was suppressed between 12 and 48 hr after implantation of 75 mg timed-release morphine pellets. Morphine suppressed NK activity in a dose-responsive manner. The opiate antagonists naloxone and naltrexone completely blocked morphine-induced suppression of NK activity, whereas naloxone methiodide, a congener that crosses the blood-brain barrier much more slowly than naloxone, produced very little blockade. Implantation of the 75-mg morphine pellets produced a significant elevation in serum corticosterone levels. In vitro exposure to corticosterone is known to suppress NK activity directly, whereas in vitro morphine was unable to alter directly NK activity. The glucocorticoid receptor antagonist Roussel-Uclaf 38486 blocked morphine-induced suppression of NK activity in a dose-responsive fashion. Naltrexone (10-mg pellet) antagonized the morphine-induced elevation in serum corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  N. Zhang, D. Hodge, T. J. Rogers, and J. J. Oppenheim Ca2+-independent Protein Kinase Cs Mediate Heterologous Desensitization of Leukocyte Chemokine Receptors by Opioid Receptors J. Biol. Chem., April 4, 2003; 278(15): 12729 - 12736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, R. Charboneau, S. Balasubramanian, R. A. Barke, H. H. Loh, and S. Roy The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the {micro}-opioid receptor J. Leukoc. Biol., May 1, 2002; 71(5): 782 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Boyadjieva, M. Dokur, J. P. Advis, G. G. Meadows, and D. K. Sarkar Chronic Ethanol Inhibits NK Cell Cytolytic Activity: Role of Opioid Peptide {beta}-Endorphin J. Immunol., November 15, 2001; 167(10): 5645 - 5652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Basso and R. A. Bornstein Neurobehavioural consequences of substance abuse and HIV infection J Psychopharmacol, May 1, 2000; 14(3): 228 - 237. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
