Ligand determinants of fatty acid activation of the pronociceptive ion channel TRPA1
William John Redmond1, Liuqiong Gu2, Maxime Camo1, Peter McIntyre2,3 and Mark Connor1
- 1 Australian School of Advanced Medicine, Macquarie University, NSW, Australia
- 2 Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia
- 3 Health Innovations Research Institute and School of Medical Sciences, RMIT University, Melbourne,
Victoria, Australia
ABSTRACT |
Background and purpose. Arachidonic acid (AA) and its derivatives are important modulators of cellular signalling. The transient receptor potential cation channel subfamily A, member 1 (TRPA1) is a cation channel with important functions in mediating cellular responses to noxious stimuli and inflammation. There is limited information about the interactions between AA itself and TRPA1, so we investigated the effects of AA and key ethanolamide and amino acid/neurotransmitter deriva- tives of AA on hTRPA1. Experimental approach. HEK 293 cells expressing hTRPA1 were studied by mea- suring changes in intracellular calcium ([Ca]i) with a fluorescent dye and by stan- dard whole cell patch clamp recordings. (300 μM) increased fluorescence by 430% (EC50, 11 μM). Anandamide (230%) and N -arachidonoyl tyrosine (170%) substantially activated hTRPA1 at 30 μM, how- ever, N -arachidonoyl conjugates of glycine and taurine were less effective while |