title: Novel synthetic sulfoglycolipid IG20 facilitates exocytosis in chromaffin cells through the regulation of sodium channels.
abstract: In search of druggable synthetic lipids that function as potential modulators of synaptic transmission and plasticity, we synthesized sulfoglycolipid IG20, which stimulates neuritic outgrowth. Here, we have explored its effects on ion channels and exocytosis in bovine chromaffin cells. IG20 augmented the rate of basal catecholamine release. Such effect did not depend on Ca(2+) mobilization from intracellular stores; rather, IG20-elicited secretion entirely dependent on Ca(2+) entry through L-subtype voltage-activated Ca(2+) channels. Those channels were recruited by cell depolarization mediated by IG20 likely through its ability to enhance the recruitment of Na(+) channels at more hyperpolarizing potentials. Confocal imaging with fluorescent derivative IG20-NBD revealed its rapid incorporation and confinement into the plasmalemma, supporting the idea that IG20 effects are exerted through a plasmalemmal-delimited mechanism. Thus, synthetic IG20 seems to mimic several physiological effects of endogenous lipids such as regulation of ion channels, Ca(2+) signaling, and exocytosis. Therefore, sulfoglycolipid IG20 may become a pharmacological tool for investigating the role of the lipid environment on neuronal excitability, ion channels, neurotransmitter release, synaptic efficacy, and neuronal plasticity. It may also inspire the synthesis of druggable sulfoglycolipids aimed at increasing synaptic plasticity and efficacy in neurodegenerative diseases and traumatic brain-spinal cord injury. The novel synthetic sulfoglycolipid IG20 mimics several physiological effects of endogenous lipids such as regulation of ion channels, Ca(2+) signaling, and exocytosis. This profile may eventually drive enhanced synaptic plasticity and efficacy.
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crespo-Castrillo
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Punzón
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Pascual
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Maroto
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: Padín
authors.affiliation: Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Álvarez
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Nanclares
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Ruiz-Pascual
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Gandía
authors.affiliation: Instituto de Quɩmica Orgánica General, CSIC, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
mesh_terms: D000818:Animals; D001393:Azoles / Q000378:metabolism / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism / Q000494:pharmacology*; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009578:Nitrobenzenes / Q000378:metabolism / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: C510797:7-nitrobenz-2-oxa-1,3-diazol-4-yl; D001393:Azoles; D002395:Catecholamines; D004791:Enzyme Inhibitors; D006017:Glycolipids; D049990:Membrane Transport Modulators; D009578:Nitrobenzenes; D015222:Sodium Channels; C011117:sulfoglycolipids; D002104:Cadmium; C049925:fura-2-am; D013779:Tetrodotoxin; D019284:Thapsigargin; D012964:Sodium; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D016257:Fura-2
keywords: calcium channel; chromaffin cell; compound IG20; exocytosis; sodium channel; sulfoglycolipid