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Pre-application of PPAR-± agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted the concentration-response curve for proton downwards, with a decrease of 36.9 ± 2.3% in the maximal current response to proton. GW7647 inhibition of proton-gated currents can be blocked by GW6471, a selective PPAR-± antagonist. Moreover, PPAR-± activation decreased the number of acidosis-evoked action potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose-dependently relieved nociceptive responses to injection of acetic acid in rats.

These results indicated that activation of peripheral PPAR-± acutely inhibited functional activity of ASICs in a non-genomic manner, which revealed a novel mechanism underlying rapid analgesia through peripheral PPAR-±.Acid-sensing ion channels (ASICs) are a family of proton-sensing channels. they are activated by lowering extracellular pH. So far, at least six different ASIC subunits derived from 4 genes have been found in mammals [ 14 ]. Most of the ASIC subunits (i.e. ASIC1a and b, ASIC2a and b, and ASIC3) are expressed in both DRG cell bodies and peripheral terminals, which contribute to proton-induced pain signaling [ 15 18 ].

Figure Figure5A 5A shows that nociceptive responses induced by converse golf le fleur acetic acid was potently blocked by pre-applied APETx2 (20 ¼M, 50 ¼l), a specific ASIC3 blocker, indicating the involvement of ASIC3 in the acidosis-induced nociception.ÿþThis list looks at the ten highest-rated and most advanced ASICS running shoes , helping you make your choice for a pair of shoes for running that will enable you to run farther, do it faster, and to feel more comfortable on the way. The Criteria for Evaluation section contains some useful information about ASICS technologies, so if you are looking for shoes with the latest [url=http://www.rbdforever.com/converse-golf ... -2683.html][img]http://www.rbdforever.com/images/a/converse golf le fleur- tech features, make sure to check that out as well.