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The FASEB Journal, Vol 2, 52-55, Copyright © 1988 by The Federation of American Societies for Experimental Biology

REVIEWS

Cross-dependence to opioid and alpha 2-adrenergic receptor agonists in NG108-15 cells

S Lee, CR Rosenberg and JM Musacchio
Department of Pharmacology, New York University Medical Center, New York 10016.

Clonidine, a partial alpha 2-agonist, has been used empirically to alleviate opiate withdrawal symptoms, but the mechanism of its effects is not completely understood. We studied the interactions of opioid and adrenergic receptor agonists in the NG108-15 cells, which are a model of opiate dependence. We determined that in these cells the adenylate cyclase (AC) [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing) overshoot response to opioid or alpha 2-agonist withdrawal can be significantly attenuated or suppressed by the other agonist. Subsequently, the AC overshoot response can be triggered with the antagonist to the second agonist to which the cells were not dependent. These results demonstrate that convergent dependence to morphine and alpha 2 agonists can occur in a homogeneous cell population without neuronal loops. Therefore, the basic mechanisms that can account for convergent dependence in this model take place at the level of intracellular regulatory pathways that do not require neuronal networks.


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H. Ammer and R. Schulz
Adenylyl Cyclase Supersensitivity in Opioid-Withdrawn NG108-15 Hybrid Cells Requires Gs but Is Not Mediated by the Gsalpha Subunit
J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 855 - 862.
[Abstract] [Full Text]


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Copyright © 1988 by The Federation of American Societies for Experimental Biology.