Neuroprotection by xenon, but not argon, involves NMDA receptor inhibition at the glycine site
Xenon inhibits the NMDA receptor by competing for the binding of the co-agonist glycine, and xenon inhibition can be prevented by elevating glycine concentrations.51, 52 In the current study we found that addition of glycine had no effect on the control OGD injury. The simplest explanation for this observation is that the concentration of endogenous glycine is just below saturating on the concentration–effect curve. However, the neuroprotective effect of xenon was completely reversed by the addition of glycine, consistent with inhibition of the NMDA receptor glycine site mediating xenon’s protective effect. In contrast, addition of glycine had no effect on neuroprotection by argon, indicating that argon acts via a different mechanism. The reversal of neuroprotection by xenon but not argon with added glycine is consistent with what we observed in an in vitro model of traumatic brain injury.26 Xenon acts at other targets, such as the two pore-domain potassium channel TREK-1 and the ATP-sensitive potassium (K-ATP) channel, but has no effect on N-type calcium channels53, 54, 55; however, our findings indicate that inhibition of the NMDA receptor glycine site is likely to play a major role in the neuroprotective effect of xenon.24, 26, 51, 52, 56, 57 The targets mediating the neuroprotective effect of argon are less clear; we have shown that argon does not inhibit NMDA receptors or activate TREK-1 channels.26 Nevertheless, other in vitro and in vivo studies with argon have identified activation of signalling pathways involving MEK-ERK 1/2 and PI3K/AKT, with up-regulation of heme-oxygenase-1.17, 58, 59 A recent study has also identified Nrf2 and the mammalian target of rapamycin (mTOR) signalling pathway as targets for argon.60 Although these studies clearly identify changes in these signalling pathways after argon treatment, it is not clear whether argon is acting on the upstream targets of these pathways.
Panowie, jak to kurła jest że w postaci niezjonizowanej to w ogóle jakoś się wiąże? I dlaczego np. krypton i hel tak nie dzialaja?