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Diterpenoids from caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor

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Summary

  1. 1.

    Three cyclic diterpenoids isolated from gorgonians of theEunicea genus and characterized as eupalmerin acetate (EUAC), 12,13-bisepieupalmerin (BEEP), and eunicin (EUNI) were found to be pharmacologically active on the nicotinic acetylcholine receptor (AChR).

  2. 2.

    The receptor from the BC3H-1 muscle cell line was expressed inXenopus laevis oocytes and studied with a two-electrode voltage clamp apparatus.

  3. 3.

    All three compounds reversibly inhibited ACh-induced currents, with IC50's from 6 to 35µM. ACh dose-response curves suggested that his inhibition was noncompetitive. The cembranoids also increased the rate of receptor desensitization.

  4. 4.

    Radioligand-binding studies using AChR-rich membranes fromTorpedo electric organ indicated that all three cembranoids inhibited high-affinity [3H]phencyclidine binding, with IC50's of 0.8, 11.6, and 63.8µM for EUNI, EUAC, and BEEP, respectively. The cembranoids at a 100µM concentration did not inhibit [α-125I]bungarotoxin binding to either membrane-bound or solubilized AChR.

  5. 5.

    It is concluded that these compounds act as noncompetitive inhibitors of peripheral AChR.

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Author notes

  1. Lian Li

    Present address: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, 10021-6390, New York, New York, USA

Authors and Affiliations

  1. Department of Biochemistry and Center for Molecular and Behavioural Neuroscience, School of Medicine, Universidad Central del Caribe, 00960, Bayamón, Puerto Rico, USA

    Vesna A. Eterović, Richard M. Hann & P. A. Ferchmin

  2. Department of Biochemistry and Biophysics, University of California, 95616, Davis, California, USA

    Lian Li, Yung-Hui Lee & Mark G. McNamee

  3. Department of Chemistry, University of Puerto Rico, Rio Piedras, 00931, Puerto Rico, USA

    Abimael D. Rodriguez

Authors
  1. Vesna A. Eterović
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  2. Richard M. Hann
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  3. P. A. Ferchmin
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  4. Abimael D. Rodriguez
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  5. Lian Li
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  6. Yung-Hui Lee
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  7. Mark G. McNamee
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Eterović, V.A., Hann, R.M., Ferchmin, P.A. et al. Diterpenoids from caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor. Cell Mol Neurobiol 13, 99–110 (1993). https://doi.org/10.1007/BF00735367

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  • DOI: https://doi.org/10.1007/BF00735367

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