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Isolation and Microsequencing of a Novel Cotinine Receptor

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Abstract

SUMMARY

1. Nicotine and its main derivative, cotinine, are reported to have distinct central activities in mammals. In this study, the cotinine receptor was separated by biochemical procedures including radio receptor, affinity-chromatography, SDS–PAGE, and N-terminal sequencing assays.

2. Consistently, the results showed that distinctive cotinine receptors exist in different tissues of mammals. In rat brain, the affinity chromatography and [125I]cotinine receptor essays were used to isolate a 40-kDa protein (p40) with higher affinity for cotinine than alpha-bungarotoxin and nicotine. The N-terminus amino acid sequences of the p40 and its internal tryptic peptides showed no identity to recently described protein sequences, with the exception of homology to the human p205 synovial fluid protein.

3. These results, in agreement with other behavioral studies, are the first molecular evidence for distinctive nicotine and cotinine receptors in mammals.

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REFERENCES

  • Anderson, D. J., and Arneric, S. P. (1994). Nicotinic receptor binding of (3H)nicotine, (3H)cytisine and (3H)methylcarbamylcholine in rat brain. Eur. J. Pharmacol. 253:261-267.

    Google Scholar 

  • Andersson, K., Jansson, A., Kuylenstierna, F., and Eneroth, P. (1993). Nicotine and its major metabolite cotinine have different effects on aldosterone and prolactin serum levels in the normal rat. Eur. J. Pharmacol. 228:305-312.

    Google Scholar 

  • Barrantes, F. J. (1997). The acetylcholine receptor ligand-gated channels as a molecular target of disease and therapeutic agents. Neurochem. Res. 22:391-400.

    Google Scholar 

  • Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Annal. Biochem. 72:249-254.

    Google Scholar 

  • Chahine, R., Aftimos, G., Wainberg, M. C., Navarro-Delmasure, C., and Abou Khalil, K. (1996). Cotinine modulates the cardiovascular effects of nicotine. Med. Sci. Res. 24:21-23.

    Google Scholar 

  • Chahine, R., Calderone, A., and Navarro-Delmasure, C. (1990). The in vitro effects of nicotine and cotinine on prostacyclin and thromboxane biosynthesis. Prostaglandins Leukotrienes Essential Fatty Acids 40:261-263.

    Google Scholar 

  • Chahine, R., Navarro-Delmasure, C., Chanh, P. H., Abou Assali, M., and Kastoun, E. (1993). Effects of nicotine and cotinine on noradrenergic transmission in the heart. Med. Sci. Res. 21:421-422.

    Google Scholar 

  • Decker, M. W., and Meyer, M. D. (1999). Therapeutic potential of neuronal nicotinic acetylcholine receptor agonists as novel analgesics. Biochem. Pharmacol. 58:917-923.

    Google Scholar 

  • Devereux, J., Harberli, P., and Smithies, O. (1984). A comprehensive set of sequencing analysis programs for the vax. Nucleic Acids Res. 12:387.

    Google Scholar 

  • Dwonski, L. P., Teng, L., Buxton, S. T., and Crooks, P. A. (1999). (S)-(_)-Cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke (3H)dopamine release from rat striatal slices in a calcium-dependent manner. J. Pharmacol Exp. Ther. 288:905-1011.

    Google Scholar 

  • Fuxe, K., Everitt, B. J., and Hökfelt, T. (1978). On the action of nicotine and cotinine on central 5-hydroxytryptamine neurons. Pharmacol. Biochem. Behav. 10:671-677.

    Google Scholar 

  • Goldberg, S. R., Risner, M. E., Stolerman, I. P., Reavill, C., and Garcha, H. S. (1989). Nicotine and some related compounds: Effects on schedule-controlled behavior and discriminative properties in the rat. Psychopharmacology 97:295-302.

    Google Scholar 

  • Hain, N. A. K., Stuhlmüller, B., Hahn, G. R., Kalden, J. R., Deutzmann, R., and Burmester, G. R. (1996). Biochemical characterization and microsequencing of a 205-kDa synovial protein stimulatory for T cells and reactive with rheumatoid factor containing sera. J. Immunol. 157:1773-1780.

    Google Scholar 

  • Hatsukami, D., Pentel, P. R., Jensen, J., Nelson, D., Allen, S. S., Goldman, A., and Rafael, D. (1998). Cotinine: Effects with and without nicotine. Psychopharmacology 135:141-150.

    Google Scholar 

  • Herzig, K. E., Callaway, E., Halliday, R., Naylor, H., and Benowitz, N. L. (1998). Effects of cotinine on information processing in non smokers. Psychopharmacology (Berl.) 135:127-132.

    Google Scholar 

  • Holloway, P. W. (1973). A simple procedure of removal of Triton X100 from protein samples. Anal. Biochem. 53:304-308.

    Google Scholar 

  • Keenan, R., Hatsukami, D., Rentel, P., Thompson, T., and Grillo, M. (1994). Pharmacodynamics of effects of cotinine in abstinent cigarette smokers. Clin. Pharmacol. Ther. 55:581-590.

    Google Scholar 

  • Kim, K. S., Borzelleca, J. F., Bowman, E. R., and McKennis, H. (1968). Effects of some nicotine metabolites and related compounds on isolated smooth muscle. J. Pharmacol. Exp. Ther. 161:59-69.

    Google Scholar 

  • Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680.

    Google Scholar 

  • Leatherbarrow, R. J. (1987). ENZFITTER: A Non-Linearly Regression Data Analysis Program for the IBM PC (and True Compatible). Elsevier, Amsterdam.

    Google Scholar 

  • Lena, C., and Changeux, J. P. (1997). Pathological mutations of nicotinic receptors and nicotine-based therapies for brain disorders. Curr. Opin. Neurobiol. 7:674-682.

    Google Scholar 

  • MacGehee, D., Heath, M. J. S., Gelber, S., Devay, P., and Role, L. W. (1995). Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 269:1692-1696.

    Google Scholar 

  • Martyn, J. A. (1995). Basic and clinical pharmacology of the acetylcholine receptor: Implication for the use of neuromuscular relaxants. Keio J. Med. 44:1-8.

    Google Scholar 

  • Marubio, L. M., del Mar Arroyo-Jimenez, M., Cordero-Erausquin, M., Lena, C., Le Novere, N., de Kerchove d'Exaerde, A., Huchet, M., Damaj, M. I., and Changeux, J. P. (1999). Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 29:805-810.

    Google Scholar 

  • Pianezza, M. L., Sellers, E. M., and Tyndale, R. F. (1998). Nicotine metabolism defect reduces smoking. Nature 393:750.

    Google Scholar 

  • Picciotto, M. R., Zoli, M., Rimondin, R., Lena, C., Marubio, L. M., Pich, E. M., Fuxe, K., and Changeux, J. P. (1998). Acetylcholine receptors containing the β-2 subunit are involved in the reinforcing properties of nicotine. Nature 39:173-177.

    Google Scholar 

  • Riah, O., Courrière, Ph., Dousset, J. C., Todeschi, N., and Labat, C. (1998). Nicotine is more efficient than cotinine at passing the blood-brain barrier in rats. Cell. Mol. Neurobiol. 18:311-318.

    Google Scholar 

  • Riah, O., Dousset, J. C., Courrière, Ph., Baziaed-Mouysset, G., and Ecalle, R. (1997). Synthesis of cotinine and cotinine N-oxide: Evaluation of their interaction with nicotine in the insecticidal activity. Nat. Prod. Lett. 11:37-45.

    Google Scholar 

  • Riah, O., Dousset, J. C., Courrière, Ph., Stigliani, J. L., Baziaed-Mouysset, G., and Belahsen, Y. (1999). Evidence that nicotine acetylcholine receptors are not the main targets of cotinine toxicity. Toxicol. Lett. 109:21-29.

    Google Scholar 

  • Risner, M. E., Cone, E. J., Benowitz, N. L., and Jacob, III, P. (1988). Effects of the stereoisomers of nicotine and nornicotine on schedule-controlled responding and physiological parameters of dogs. J. Pharmacol. Exp. Ther. 244:807-813.

    Google Scholar 

  • Risner, M. E., Goldberg, S. R., Prada, J. A., and Cone, E. J. (1985). Effects of nicotine, cocaine and some of their metabolites on schedule-controlled responding by beagle dogs and squirrel monkeys. J. Pharmacol. Exp. Ther. 244:807-813.

    Google Scholar 

  • Role, L. W. (1992). Diversity in primary structure and function of neuronal nicotinic acetylcholine receptor channels. Curr. Opin. Neurobiol. 2:254-262.

    Google Scholar 

  • Romano, C., and Goldstein, A. (1980). Stereospecific nicotine receptors in rat brain membranes. Sciences 210:647-650.

    Google Scholar 

  • Sargent, P. B. (1993). The diversity of neuronal nicotinic acetylcholine receptors. Annu. Rev. Neurosci 16:403-443.

    Google Scholar 

  • Sloan, J. W., Todd, J. D., and Martin, W. R. (1984). Nature of nicotine binding to rat brain P2 fraction. Pharmacol. Biochem. Behav. 20:899-909.

    Google Scholar 

  • Vainio, P. J., Viluksela, M., Tuominen, R. K. (1998). Nicotine-like effects of cotinine on protein kinase C activity and noradrenaline release in bovine adrenal chromaffin cells. J. Auton. Pharmacol. 18:245-250.

    Google Scholar 

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Author notes

  1. Elisa Bofill-Cardona

    Present address: Institute of Pharmacology, Vienna University, A 1090, Vienna, Austria

Authors and Affiliations

  1. Faculté des Sciences Pharmaceutiques, Laboratoire des Mécanismes d'Action des Nicotianées, 35, Chemin des Maraichers, 31062, Toulouse Cedex, France

    Omar Riah, Jean-Claude Dousset, Elisa Bofill-Cardona & Philippe Courrière

  2. Département de Biologie, Faculté des Sciences, Laboratoire de Biochimie, BP 32/S, 7000, Agadir, Maroc

    Omar Riah

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  1. Omar Riah
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  2. Jean-Claude Dousset
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  3. Elisa Bofill-Cardona
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  4. Philippe Courrière
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Riah, O., Dousset, JC., Bofill-Cardona, E. et al. Isolation and Microsequencing of a Novel Cotinine Receptor. Cell Mol Neurobiol 20, 653–664 (2000). https://doi.org/10.1023/A:1007094623775

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