title: Membrane-mediated action of the endocannabinoid anandamide on membrane proteins: implications for understanding the receptor-independent mechanism.
abstract: 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.
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.|Curso de Filosofia, Faculdade de São Bento, São Paulo, SP, Brasil.
authors.forename: Djalma
authors.initials: D
authors.lastname: Medeiros
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: Laíz da Costa
authors.initials: LC
authors.lastname: Silva-Gonçalves
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: Annielle Mendes Brito
authors.initials: AM
authors.lastname: da Silva
authors.affiliation: Departamento de Química e Ciências Ambientais, IBILCE, Universidade Estadual Paulista, São José do Rio Preto, SP, Brasil.
authors.forename: Marcia Perez
authors.initials: MP
authors.lastname: Dos Santos Cabrera
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: Manoel
authors.initials: M
authors.lastname: Arcisio-Miranda
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D063388:Endocannabinoids / Q000494:pharmacology*; D006096:Gramicidin / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D006096:Gramicidin; C017251:1,2-oleoylphosphatidylcholine; C078814:anandamide