The use of nonneuronal cells as an in vitro model system for studying the genetic component of cellular response to opiates and other drugs of abuse.
Nonneuronal cells, such as the human T lymphocyte, react directly with opiates in vitro causing significant alterations in the metabolism of these cells. Morphine and cocaine, for example, can modulate the repair of DNA damage caused by ultraviolet light (UVC)--morphine in the negative direction and cocaine in the positive. The mechanism by which these drugs cause these metabolic changes is not yet known, but a simple receptor mechanism such as is found in the central nervous system (CNS) can not be demonstrated. Binding studies using lymphocyte membrane preparations or whole cells do not support the premise that T lymphocytes have opiate binding sites with specificities comparable to those identified in the CNS--the mu, delta and kappa receptors. Even without knowing the mechanism for the opiate-induced metabolic changes, the alterations can be used as the basis for a test of the genetics of opiate metabolism. If the interindividual variation in the opiate-induced repair response is greater than the intraindividual variation as assessed by repeated measures on the same subject, it may be possible to utilize this assay in the classic sorts of family or twin studies to determine the genetic component of the response to opiates.
Madden
J J
JJ
Department of Psychiatry, Emory University, Atlanta, GA 30322.
Falek
A
A
D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000235:genetics*; D011957:Receptors, Opioid / Q000235:genetics*; D019966:Substance-Related Disorders / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects*
D009294:Narcotics; D011957:Receptors, Opioid; D003042:Cocaine