Membrane-mediated action of the endocannabinoid anandamide on membrane proteins: implications for understanding the receptor-independent mechanism

Autor(es)

Medeiros, Djalma ; Silva-Goncalves, Laiz da Costa ; Brito da Silva, Annielle Mendes ; dos Santos Cabrera, Marcia Perez ; Arcisio-Miranda, Manoel

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, JAN 27 2017.
• Citações Web of Science: 2

Resumo

Endocannabinoids are amphiphilic molecules that play crucial neurophysiological functions acting as lipid messengers. Antagonists and knockdown of the classical CB1 and CB2 cannabinoid receptors do not completely abolish many endocannabinoid activities, supporting the idea of a mechanism independent of receptors whose mode of action remains unclear. Here we combine gramicidin A (gA) single channel recordings and membrane capacitance measurements to investigate the lipid bilayer-modifying activity of endocannabinoids. Single channel recordings show that the incorporation of endocannabinoids into lipid bilayers reduces the free energy necessary for gramicidin channels to transit from the monomeric to the dimeric conformation. Membrane capacitance demonstrates that the endocannabinoid anandamide has limited effects on the overall structure of the lipid bilayers. Our results associated with the theory of membrane elastic deformation reveal that the action of endocannabinoids on membrane proteins can involve local adjustments of the lipid/protein hydrophobic interface. The current findings shed new light on the receptor-independent mode of action of endocannabinoids on membrane proteins, with important implications towards their neurobiological function. (AU)

• Processo FAPESP: 12/02065-0 - Eletrofisiologia de peptídeos antimicrobianos em bicamadas lipídicas planas
• Beneficiário: Manoel de Arcisio Miranda Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/24259-0 - Moléculas conjugadas peptídeo/quitosana com potencial farmacológico: síntese, prospecção de atividade em sistemas miméticos de membrana e avaliações em células
• Beneficiário: Marcia Perez dos Santos Cabrera
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/08372-7 - Moléculas conjugadas peptídeo/quitosana com potencial farmacologico: síntese, prospecção de atividade em sistemas mimeticos de membrana e avaliações em células
• Beneficiário: Marcia Perez dos Santos Cabrera
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores