Home > Articles > Published articles > Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors : |
Date: | 2017 |
Abstract: | Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into in vitro and in vivo receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice. The combination of light and some specific phenylazopyridine ligands displays atypical pharmacological profiles, including light-dependent receptor overactivation, which can be observed both in vitro and in vivo. Remarkably, the localized administration of light and a photoswitchable compound in the peripheral tissues of rodents or in the brain amygdalae results in an illumination-dependent analgesic effect. The results reveal a robust translation of the phenylazopyridine photoisomerization to a precise photoregulation of biological activity. The cis − trans photoisomerization of phenylazopyridines, allowing mGlu receptor activity photoswitching in cells, is used in vivo to control zebrafish motility with light and analgesia in mice including peripheral and brain localized illumination. |
Grants: | Ministerio de Economía y Competitividad CTQ2014-57020-R Ministerio de Economía y Competitividad PCIN-2013-017-C03-01 Ministerio de Economía y Competitividad PIE14/00034 Ministerio de Economía y Competitividad SAF2014-55700-P Ministerio de Economía y Competitividad PCIN-2013-019-C03-03 Ministerio de Economía y Competitividad SAF2014-58396-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2010/BP-A 00194 Agència de Gestió d'Ajuts Universitaris i de Recerca 2012/FI_B 01122 Agència de Gestió d'Ajuts Universitaris i de Recerca 2012/CTP 00033 Agència de Gestió d'Ajuts Universitaris i de Recerca 2012/BE1 00597 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1251 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-00109 |
Note: | This is an open access article published under an ACS AuthorChoice License. See Standard ACS AuthorChoice/Editors' Choice Usage Agreement - https://pubs.acs.org/page/policy/authorchoice_termsofuse.html |
Rights: | Tots els drets reservats. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Published in: | ACS Central Science, Vol. 3, issue 1 (Jan. 2017) , p. 81-91, ISSN 2374-7951 |
11 p, 2.3 MB |