T-type calcium channel inhibition underlies the analgesic effects of the endogenous lipoamino acids. The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] Journal article

Title	T-type calcium channel inhibition underlies the analgesic effects of the endogenous lipoamino acids.
Author(s)	Barbara G, Alloui A, Nargeot J, Lory P, Eschalier A, Bourinet E, Chemin J
Institution	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.
Source	J Neurosci 2009 Oct 21; 29(42):13106-14.
MeSH	Analgesics Animals Arachidonic Acids Behavior, Animal Calcium Calcium Channel Blockers Calcium Channels, L-Type Calcium Channels, T-Type Cells, Cultured Disease Models, Animal Electric Stimulation Ganglia, Spinal Glycine Green Fluorescent Proteins Humans Hyperalgesia Male Membrane Potentials Mice Mice, Inbred C57BL Mice, Knockout Morphine Nerve Tissue Proteins Neuroblastoma Patch-Clamp Techniques Potassium Channels, Tandem Pore Domain Sensory Receptor Cells Sodium Channels TRPV Cation Channels Transfection gamma-Aminobutyric Acid
Abstract	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.
Language	eng
Pub Type(s)	Journal Article Research Support, Non-U.S. Gov't
PubMed ID	19846698

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