       Document 1143
 DOCN  M9591143
 TI    Antiproliferative effects of delta opioids on highly purified CD4+ and
       CD8+ murine T cells.
 DT    9509
 AU    Shahabi NA; Sharp BM; Endocrine-Neuroscience Research Laboratory,
       Minneapolis Medical; Research Foundation, Minnesota, USA.
 SO    J Pharmacol Exp Ther. 1995 Jun;273(3):1105-13. Unique Identifier :
       AIDSLINE MED/95311171
 AB    Numerous studies have shown that opioids modulate the proliferative
       response of mixed splenocytes to T cell mitogens. To identify the T cell
       subpopulations affected by opioids, splenocytes from C57BL/6 and CD1
       mice were separated using a fluorescent activated cell sorter (FACS) to
       obtain 98 to 99% pure populations of either CD4+ or CD8+ T cells. Cells
       were stimulated to proliferate in serum-free medium by cross-linking the
       T cell receptor using plate-coated anti-CD3-epsilon, then 3H-thymidine
       uptake and cell number were measured at 48 and 72 hr.
       [D-Ala2]-deltorphin 1 (deltorphin) dose-dependently inhibited the
       proliferation of C57BL/6 CD4+ T cells by approximately 50%. This effect
       was maximal when cells were preincubated with deltorphin 60 min before
       activation, whereas deltorphin was ineffective when added at the time of
       activation. Similarly, [D-Ala2]-Met-Enkephalinamide (DAME) 10(-11) to
       10(-7) M inhibited CD4+ T cell proliferation. Naltrindole 10(-12) M
       abolished the antiproliferative effect of 10(-7) M deltorphin on CD4+ T
       cells. Proliferation of CD8+ T cells from C57BL/6 mice also was
       dose-dependently inhibited by deltorphin. At all concentrations to
       deltorphin, the antiproliferative effects were greater after 48 compared
       to 72 hr in culture. The effect of deltorphin and DAME on secretion of
       the T cell growth factor, IL-2, was determined by ELISA analysis of
       supernatants obtained from CD4+ T cells after 48-hr culture. Deltorphin
       showed a biphasic effect: 10(-11) M enhanced IL-2 secretion, whereas
       higher concentrations (10(-9)-10(-7) M) were inhibitory.(ABSTRACT
       TRUNCATED AT 250 WORDS)
 DE    Animal  Cell Division/DRUG EFFECTS  Cell Separation  CD4-Positive
       T-Lymphocytes/CYTOLOGY/*DRUG EFFECTS  CD8-Positive
       T-Lymphocytes/CYTOLOGY/*DRUG EFFECTS  Female  Flow Cytometry  Mice
       Mice, Inbred C57BL  Narcotics/*PHARMACOLOGY  Receptors, Opioid,
       delta/*AGONISTS  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

