Modulation of thymidine incorporation by kappa-opioid ligands in rat spinal cord-dorsal root ganglion co-cultures.
beta-Endorphin, met-enkephalin and several mu-selective opioid agonists were shown to decrease thymidine incorporation into DNA in various neural cell cultures. We now report that the kappa-selective opioid agonists U50488, U69593 and MR2034 modulate [3H]thymidine incorporation into DNA in rat spinal cord-dorsal root ganglion co-cultures. U50488 at 10 microM increased by 60% thymidine incorporation in 6-day-old cultures. The thymidine incorporation induced by U50488 was blocked by the kappa-selective antagonist nor-binaltorphimine, as well as by pertussis toxin and LiCl. U50488 treatment stimulated phosphatidylinositol turnover by three-fold compared with untreated controls. These findings suggest that kappa-opioid agonists modulate DNA synthesis in spinal cord-dorsal root ganglion co-cultures through a mechanism which involves pertussis toxin-sensitive GTP-binding proteins, as well as activation of phosphatidylinositol turnover.
Barg
J
J
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Nah
S Y
SY
Levy
R
R
Saya
D
D
Vogel
Z
Z
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000494:pharmacology*; D002450:Cell Communication; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D018021:Lithium Chloride / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000700:Analgesics; D044482:Benzeneacetamides; D001575:Benzomorphans; D007295:Inositol Phosphates; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D010566:Virulence Factors, Bordetella; D014316:Tritium; C032478:MR 2034; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004247:DNA; D037342:Pertussis Toxin; D018021:Lithium Chloride; C045444:U 69593; D013936:Thymidine