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reebok classic
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Thomas Emma 
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Dołączyła: 24 Kwi 2020
Posty: 3
Wysłany: Pią Kwi 24, 2020 3:56 am   reebok classic

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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 reebok pump 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 ]. It is known that pain can be produced by tissue acidosis. Protons depolarize DRG neurons and generate action potenials through activating ASICs. For instance, direct application of an acidic solution into the skin induces non-adapting pain [ 19 ].

Above results indicated that activity reebok shoes of ASICs was inhibited by GW7647 in vitro . We finally determined whether GW7647 inhibition of ASICs was involved in pain-related behaviors in vivo . Rats displayed an intense flinch/shaking responses after acetic acid (0.6%) was injected into hindpaws. The nociceptive responses mainly occurred during 0-5 min after intraplantar injection of acetic acid [ 16 , 34 ]. We measured the number of flinches that rats spent licking and/or lifting the injected hindpaws. Figure 5A shows that nociceptive responses induced by 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.

Our electrophysiological and behavioral evidence demonstrated that PPAR-± activation can acutely inhibit the activity of ASICs in nociceptive DRG neurons. PPAR-± agonist GW7647 decreased the amplitude of proton-activated currents and acidosis-triggered action potentials in rat isolated DRG neurons. Peripheral administration of GW7647 relieved acidosis-evoked nociceptive responses and CFA-induced mechanical hypersensitivity in rats.

GW7647 shifted the proton concentration response curve downward and reebok cross trainers decreased the maximum response without changing the IC 50 values, indicating that PPAR-± activation resulted in a decrease in the efficiency of ASICs and had no effect on the affinity of ASICs for protons. ASICs are mostly permeable to Na , activation of these channels can thus depolarize membrane potentials to the threshold of excitability and result in bursts of action potentials [ 37 ]. Data from current clamp experiments revealed that acidosis-triggered action potentials were also inhibited by GW7647. This decreased neuronal excitability may correlate with results that ASIC currents were attenuated by GW7647 in voltage clamp experiments.
 
     
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