| T-type calcium channel inhibition underlies the analgesic effects of the endogenous lipoamino acids. | |
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MedLine Citation:
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PMID: 19846698 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipoamino acids are anandamide-related endogenous molecules that induce analgesia via unresolved mechanisms. Here, we provide evidence that the T-type/Cav3 calcium channels are important pharmacological targets underlying their physiological effects. Various lipoamino acids, including N-arachidonoyl glycine (NAGly), reversibly inhibited Cav3.1, Cav3.2, and Cav3.3 currents, with potent effects on Cav3.2 [EC(50) approximately 200 nm for N-arachidonoyl 3-OH-gamma-aminobutyric acid (NAGABA-OH)]. This inhibition involved a large shift in the Cav3.2 steady-state inactivation and persisted during fatty acid amide hydrolase (FAAH) inhibition as well as in cell-free outside-out patch. In contrast, lipoamino acids had weak effects on high-voltage-activated (HVA) Cav1.2 and Cav2.2 calcium currents, on Nav1.7 and Nav1.8 sodium currents, and on anandamide-sensitive TRPV1 and TASK1 currents. Accordingly, lipoamino acids strongly inhibited native Cav3.2 currents in sensory neurons with small effects on sodium and HVA calcium currents. In addition, we demonstrate here that lipoamino acids NAGly and NAGABA-OH produced a strong thermal analgesia and that these effects (but not those of morphine) were abolished in Cav3.2 knock-out mice. Collectively, our data revealed lipoamino acids as a family of endogenous T-type channel inhibitors, suggesting that these ligands can modulate multiple cell functions via this newly evidenced regulation. |
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Authors:
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Guillaume Barbara; Abdelkrim Alloui; Joël Nargeot; Philippe Lory; Alain Eschalier; Emmanuel Bourinet; Jean Chemin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 29 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-22 Completed Date: 2009-11-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 13106-14 Citation Subset: IM |
Affiliation:
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Département de Physiologie, Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5203, INSERM U661, Universités de Montpellier, 34094 Montpellier, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analgesics
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pharmacology* Animals Arachidonic Acids / pharmacology* Behavior, Animal / physiology Calcium / metabolism Calcium Channel Blockers / pharmacology Calcium Channels, L-Type / genetics Calcium Channels, T-Type / classification, genetics, metabolism* Cells, Cultured Disease Models, Animal Electric Stimulation / methods Ganglia, Spinal / cytology Glycine / analogs & derivatives*, pharmacology Green Fluorescent Proteins / genetics Humans Hyperalgesia / drug therapy, genetics Male Membrane Potentials / drug effects, genetics Mice Mice, Inbred C57BL Mice, Knockout Morphine / pharmacology Nerve Tissue Proteins / genetics Neuroblastoma Patch-Clamp Techniques / methods Potassium Channels, Tandem Pore Domain / genetics Sensory Receptor Cells Sodium Channels / genetics TRPV Cation Channels / genetics Transfection gamma-Aminobutyric Acid / analogs & derivatives*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Analgesics; 0/Arachidonic Acids; 0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Calcium Channels, T-Type; 0/N-arachidonoyl-gamma-amino-butyric acid; 0/N-arachidonylglycine; 0/Nerve Tissue Proteins; 0/Potassium Channels, Tandem Pore Domain; 0/SCN9A protein, human; 0/Sodium Channels; 0/TRPV Cation Channels; 0/TRPV1 protein, human; 0/potassium channel subfamily K member 3; 147336-22-9/Green Fluorescent Proteins; 56-12-2/gamma-Aminobutyric Acid; 56-40-6/Glycine; 57-27-2/Morphine; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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