GLIAL GROWTH IS REGULATED BY AGONISTS SELECTIVE FOR MULTIPLE OPIOID RECEPTOR TYPES INVITRO

被引:58
作者
STIENEMARTIN, A
HAUSER, KF
机构
[1] UNIV KENTUCKY, SCH MED,MED CTR,DEPT ANAT & NEUROBIOL,800 ROSE ST, LEXINGTON, KY 40536 USA
[2] UNIV KENTUCKY, SCH MED, MED CTR, DEPT CLIN SCI, LEXINGTON, KY 40536 USA
关键词
ENDOGENOUS OPIOID SYSTEMS; ASTROCYTE; GLIAL DEVELOPMENT; CELL PROLIFERATION; OPIOID RECEPTOR TYPES; DRUG ABUSE;
D O I
10.1002/jnr.490290415
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To determine whether one or more opioid receptor types might be preferentially involved in gliogenesis, primary mixed glial cultures derived from mouse cerebra were continuously treated with varying concentrations of opioid agonists selective for mu (mu), i.e., DAGO ([D-Ala2, MePhe4, Gly(ol)5]enkephalin), delta (delta), i.e., DPDPE ([D-PEN2,D-PEN5]enkephalin), or kappa (kappa), i.e., U69,593, opioid receptor types. In addition, a group of cultures was treated with [Met5]enkephalin, an agonist for delta-opioid receptors as well as putative zeta (zeta) opioid receptors. Opioid-dependent changes in growth were assessed by examining alterations in (1) the number of cells in mixed glial cultures at 3, 6, and 8 days in vitro (DIV), (2) [3 H]thymidine incorporation by glial fibrillary acidic protein (GFAP) immunoreactive, flat (type 1) astrocytes at 6 DIV, and (3) the area and form factor of GFAP-immunoreactive, flat (type 1) astrocytes. DPDPE at 10(-8) or 10(-10) M, as well as [Met5]enkephalin at 10(-6), 10(-8), or 10(-10) M, significantly reduced the total number of glial cells in culture; but this effect was not observed with DAGO or U69,593 (both at 10(-6), 10(-8), or 10(-10) M). Equimolar concentrations (i.e., 10(-6) M) of [Met5]enkephalin or U69,593, but not DPDPE or DAGO, suppressed the rate of [H-3]thymidine incorporation by GFAP-immunoreactive, flat (type 1) astrocytes. DAGO had no effect on growth, although in previous studies morphine was found to inhibit glial numbers and astrocyte DNA synthesis. [Met5]enkephalin (10(-6) M) was the only agonist to significantly influence astrocyte area. Collectively, these results indicate that delta (and perhaps-mu) opioid receptor agonists reduce the total number of cells in mixed glial cultures; while [Met5]enkephalin-responsive (and perhaps kappa-responsive) opioid receptors mediate DNA synthesis in astrocytes. This implies that delta-opioid receptors, as well as [Met5]enkephalin-sensitive, non-delta-opioid receptors, mediate opioid-dependent regulation of astrocyte and astrocyte progenitor growth. These data support the concept that opioid-dependent changes in central nervous system growth are the result of endogenous opioid peptides acting through multiple opioid receptor types.
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页码:538 / 548
页数:11
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