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1.
Pflugers Arch ; 466(7): 1421-35, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24114173

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.


Assuntos
Potenciais de Ação , Ácidos Araquidônicos/metabolismo , Cálcio/metabolismo , Endocanabinoides/metabolismo , Fosfatidiletanolaminas/farmacologia , Alcamidas Poli-Insaturadas/metabolismo , Células Receptoras Sensoriais/metabolismo , 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
2.
Acta Crystallogr B ; 61(Pt 6): 663-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16306673

RESUMO

Detailed structures of nonasodium tetrakis(sulfate) chloride diperhydrate, Na9[SO4]4Cl.2H2O2, and its novel bromide analogue are compared. Hydrogen peroxide could not be resolved in a previously reported Na9[SO4]4Cl.2H2O2 substructure. However, on lowering the symmetry to P4/n, and using reflection data based on full unit-cells, the H2O2 solvate can be clearly seen. Although H2O2 molecules are not directly bonded to the halide anions, they exert considerable influence on the eight sodium cations that constitute each halide's coordination shell so that H2O2 ordering can be linked to halide dimensions.

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