Alcohol-, nicotine-, and cocaine-evoked release of morphine from human white blood cells: Substances of abuse actions converge on endogenous morphine release

Background: Normal human white blood cells (WBC) have the ability to synthesize morphine as do invertebrate
ganglia. Furthermore, invertebrate neural tissues incubated with ethanol, cocaine, or nicotine results
in a statistically signifi cant enhancement of labeled morphine release. We now demonstrate that this also occurs with human WBC.
Matreial/Methods: Human blood was obtained from the Long Island Blood Services (Melville, NY). Polymorphonuclear cells (PMN) or mononuclear cells (MN) (10 million/ml) were bathed in phosphate buffered saline(PBS) medium containing purifi ed RIA grade [sup]125[/sup]I-labeled morphine for trace labeling and quantifi cation of media concentrations of morphine were via RIA. Cells were then incubated with cocaine, alcohol or nicotine and morphine release was determined. Residual levels of radioactivity in control tissues were always greater than 65% of total cpm, whereas in treated tissue differences depended on the amount of drug added.
Results: Incorporation rates of [sup]125[/sup]I-labeled morphine into PMN and MN were 7.85±0.36% and 1.42±0.19%, respectively. Separate incubations of PMN with ethanol, cocaine, or nicotine resulted in a statistically signifi cant enhancement of ,sup>125[/sup]I-labeled morphine released into the extracellular medium in a concentration dependent manner.
Conclusions: These substances of abuse have been linked into a common pathway because of the common
dopamine connection. Now, they are additionally linked because of their common effect on endogenous
morphinergic processes. It is highly signifi cant that these substances of abuse converge on a similar process, providing a mechanism to initiate their pleasure and addicting actions with
continued frequent use.

Keywords: Dose-Response Relationship, Drug, Cocaine - pharmacology, Alcohols - pharmacology, Iodine Radioisotopes - pharmacology, Leukocytes - metabolism, Leukocytes, Mononuclear - metabolism, Morphine - pharmacokinetics, Neutrophils - cytology, Nicotine - pharmacology, Radioimmunoassay, Substance-Related Disorders - metabolism