| [PMID]: | 24114173 |
| [Au] Autor: | Varga A; Jenes A; Marczylo TH; Sousa-Valente J; Chen J; Austin J; Selvarajah S; Piscitelli F; Andreou AP; Taylor AH; Kyle F; Yaqoob M; Brain S; White JP; Csernoch L; Di Marzo V; Buluwela L; Nagy I |
| [Ad] Endereço: | Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK. |
| [Ti] Título: | Anandamide produced by Ca(2+)-insensitive enzymes induces excitation in primary sensory neurons. |
| [So] Source: | Pflugers Arch;466(7):1421-35, 2014 Jul. |
| [Is] ISSN: | 1432-2013 |
| [Cp] País de publicação: | Germany |
| [La] Idioma: | eng |
| [Ab] Resumo: | The endogenous lipid agent N-arachidonoylethanolamine (anandamide), among other effects, has been shown to be involved in nociceptive processing both in the central and peripheral nervous systems. Anandamide is thought to be synthesised by several enzymatic pathways both in a Ca(2+)-sensitive and Ca(2+)-insensitive manner, and rat primary sensory neurons produce anandamide. Here, we show for the first time, that cultured rat primary sensory neurons express at least four of the five known Ca(2+)-insensitive enzymes implicated in the synthesis of anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl, the common substrate of the anandamide-synthesising pathways, results in anandamide production which is not changed by the removal of extracellular Ca(2+). We also show that anandamide, which has been synthesised in primary sensory neurons following the application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl induces a transient receptor potential vanilloid type 1 ion channel-mediated excitatory effect that is not inhibited by concomitant activation of the cannabinoid type 1 receptor. Finally, we show that sub-populations of transient receptor potential vanilloid type 1 ion channel-expressing primary sensory neurons also express some of the putative Ca(2+)-insensitive anandamide-synthesising enzymes. Together, these findings indicate that anandamide synthesised by primary sensory neuron via a Ca(2+)-insensitive manner has an excitatory rather than an inhibitory role in primary sensory neurons and that excitation is mediated predominantly through autocrine signalling. Regulation of the activity of the Ca(2+)-insensitive anandamide-synthesising enzymes in these neurons may be capable of regulating the activity of these cells, with potential relevance to controlling nociceptive processing. |
| [Mh] Termos MeSH primário: |
Potenciais de Ação
Ácidos Araquidônicos/metabolismo
Cálcio/metabolismo
Endocanabinoides/metabolismo
Fosfatidiletanolaminas/farmacologia
Alcamidas Poli-Insaturadas/metabolismo
Células Receptoras Sensoriais/metabolismo
|
| [Mh] Termos MeSH secundário: |
Animais
Ácidos Araquidônicos/biossíntese
Células Cultivadas
Endocanabinoides/biossíntese
Gânglios Espinais/citologia
Gânglios Espinais/enzimologia
Gânglios Espinais/metabolismo
Fosfolipases A2 do Grupo IB/genética
Fosfolipases A2 do Grupo IB/metabolismo
Lisofosfolipase/genética
Lisofosfolipase/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Fosfatidiletanolaminas/química
Diester Fosfórico Hidrolases/genética
Diester Fosfórico Hidrolases/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 22/genética
Proteína Tirosina Fosfatase não Receptora Tipo 22/metabolismo
Ratos
Ratos Sprague-Dawley
Células Receptoras Sensoriais/enzimologia
Células Receptoras Sensoriais/fisiologia
Canais de Cátion TRPV/genética
Canais de Cátion TRPV/metabolismo
|
| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl); 0 (Arachidonic Acids); 0 (Endocannabinoids); 0 (Phosphatidylethanolamines); 0 (Polyunsaturated Alkamides); 0 (TRPV Cation Channels); 0 (TRPV1 protein, mouse); EC 3.1.1.4 (Group IB Phospholipases A2); EC 3.1.1.5 (Lysophospholipase); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 22); EC 3.1.4.- (Phosphoric Diester Hydrolases); EC 3.1.4.46 (glycerophosphodiester phosphodiesterase); SY7Q814VUP (Calcium); UR5G69TJKH (anandamide) |
| [Em] Mês de entrada: | 1502 |
| [Cu] Atualização por classe: | 171005 |
[Lr] Data última revisão:
| 171005 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 131012 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1007/s00424-013-1360-7 |
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