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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

New insights in the mode of action of (+)-erythravine and (+)-11 alpha-hydroxy-erythravine alkaloids

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Author(s):
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Gelfuso, Erica A. [1, 2] ; Reis, Suelen L. [1] ; Aguiar, Daiane S. R. [1] ; Faggion, Silmara A. [1] ; Gomes, Flavia M. M. [3] ; Galan, Diogo T. [4] ; Peigneur, Steve [4] ; Pereira, Ana M. S. [1] ; Mortari, Marcia R. [3] ; Cunha, Alexandra O. S. [5] ; Tytgat, Jan [4] ; Beleboni, Rene O. [1, 6]
Total Authors: 12
Affiliation:
[1] Univ Ribeirao Preto, Dept Biotechnol, Ribeirao Preto, SP - Brazil
[2] Univ Rennes, CHU Rennes, INSERM, LTSI Lab Traitement Signal & Image, UMR 1099, F-35000 Rennes - France
[3] Univ Brasilia, Neuropharmacol Lab, Dept Physiol Sci, Inst Biol Sci, Brasilia, DF - Brazil
[4] Univ Leuven KU Leuven, Toxicol & Pharmacol, Leuven - Belgium
[5] Univ Sao Paulo, Dept Physiol, FMRP, Ribeirao Preto, SP - Brazil
[6] Univ Ribeirao Preto, Sch Med, Ribeirao Preto, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: European Journal of Pharmacology; v. 885, OCT 15 2020.
Web of Science Citations: 0
Abstract

Erythrinian alkaloids ((+)-erythravine and (+)-11-alpha-hydroxy-erythravine) have been pointed as the main responsible agents for the anticonvulsant and anxiolytic properties of Erythrina mulungu Mart ex Benth. The present work provides a new set of information about the mode of action of these alkaloids by the use of a complementary approach of neurochemical and electrophysiological assays. We propose here that the antiepileptic and anxiolytic properties exhibited by both alkaloids appear not to be related to the inhibition of glutamate binding or GABA uptake, or even to the increase of glutamate uptake or GABA binding, as investigated here by the use of rat cortical synaptosomes. Similarly, and even in a high concentration, (+)-erythravine and (+)-11-alpha-hydroxy-erythravine did not modulate the main sodium and potassium channel isoforms checked by the use of voltage-clamp studies on Xenopus laeyis oocytes. However, unlike (+)-11-alpha- hydroxy-erythravine, which presented a little effect, it was possible to observe that the (+)-erythravine alkaloid produced a significant inhibitory modulation on alpha(4)beta(2), alpha(4)beta(4) and alpha(7) isoforms of nicotinic acetylcholine receptors also checked by the use of voltage-clamp studies, which could explain at least partially its anxiolytic and anticonvulsant properties. Since (+)-11-alpha-hydroxy-erythravine and (+)-erythravine modulated nicotinic acetylcholine receptors to different extents, it is possible to reinforce that small differences between the chemical structure of these alkaloids can affect the selectivity and affinity of target-ligand interactions, conferring distinct potency and/or pharmacological properties to them, as previously suggested by differential experimental comparison between different erythrinian alkaloids. (AU)