Delta opioid peptide DADLE and naltrexone cause cell cycle arrest and differentiation in a CNS neural progenitor cell line.
Opioids have been demonstrated to play an important role in CNS development by affecting proliferation and differentiation in various types of neural cells. This study examined the effect of a stable delta opioid peptide [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) on proliferation and differentiation in an AF5 CNS neural progenitor cell line derived from rat mesencephalic cells. DADLE (1 pM, 0.1 nM, or 10 nM) caused a significant growth inhibition on AF5 cells. The opioid antagonist naltrexone at 0.1 nM also caused growth inhibition in the same cells. When DADLE and naltrexone were both added to the AF5 cells, the resultant growth inhibition was apparently additive. DADLE alone or DADLE in combination with naltrexone did not cause apoptosis as evidenced by negative TUNEL staining. The cell-cycle progression analysis indicated that both DADLE (0.1 nM) and naltrexone (0.1 nM) caused an arrest of AF5 cell cycle progression at the G1 checkpoint. Neuronal marker indicated that DADLE- or naltrexone-treated AF5 cells tend to differentiate more when compared to controls. Results demonstrate the nonopioid action of both DADLE and naltrexone on cell cycle arrest and differentiation in a CNS neural progenitor cell line. Results also suggest some potential utilization of DADLE and/or naltrexone in stem cell research.
Tsai
Shang-Yi
SY
Cellular Pathobiology Section, Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, Maryland 21224, USA.
Lee
Chung-Ting
CT
Hayashi
Teruo
T
Freed
William J
WJ
Su
Tsung-Ping
TP
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D005434:Flow Cytometry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000187:drug effects*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C034641:naltrexazone