Tobacco Cembranoids Block Behavioral Sensitization To Nicotine And Inhibit Neuronal Acetylcholine Receptor Function
Cembranoids are cyclic diterpenoids found in tobacco and in marine invertebrates. The present study established that tobacco cembranoids inhibit behavioral sensitization to nicotine in rats and block several types of nicotine acetylcholine receptors (AChRs). 1) At the behavioral level, rat locomotor activity induced by nicotine was significantly increased after seven daily nicotine injections. This sensitization to nicotine was blocked by mecamylamine (1 mg/kg) and by the cembranoids eunicin, eupalmerin acetate (EUAC), and (4R)-2,7,11-cembratriene-4-6-diol (4R), each at 6 mg/kg. None of these compounds modified locomotor activity of non-sensitized rats. 2) In cells expressing human AChRs, cembranoids blocked carbamoylcholine-induced 86Rb+ flux with IC50 in the low micromolar range. The cell lines used were the SH-EP1-hÎ±4Î²2 cell line heterologously expressing human Î±4Î²2-AChR, the SH-SY5Y neuroblastoma line naturally expressing human ganglionic Î±3Î²4-AChR, and the TE671/RD cell line naturally expressing embryonic muscle Î±1Î²1Î³Î´-AChR. The tobacco cembranoids tested were 4R and its diastereoisomer 4S, and marine cembranoids tested were EUAC and 12,13-bisepieupalmerin. 3) At the molecular level, tobacco (4R and 4S) and marine (EUAC) cembranoids blocked binding of the noncompetitive inhibitor [3H]tenocyclidine to AChR from Torpedo californica electric organ. IC50 values were in the submicromolar to low-micromolar range, with 4R displaying an order of magnitude higher potency than its diastereoisomer, 4S. Â© 2001 Wiley-Liss, Inc.
Journal of Neuroscience Research
Digital Object Identifier (DOI)
Ferchmin, P. A.; Lukas, R. J.; Hann, R. M.; Fryer, J. D.; Eaton, J. B.; Pagn, O. R.; RodrÃguez, A. D.; Nicolau, Y.; Rosado, M.; CortÃ©s, S.; and Eterovi, V. A., "Tobacco Cembranoids Block Behavioral Sensitization To Nicotine And Inhibit Neuronal Acetylcholine Receptor Function" (2001). Translational Neuroscience. 286.