IndraLab

Statements

Spadin inhibits KCNK2. 11 / 11
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"The difference in findings between the two independent studies is likely due to the varied approaches that were used for TREK-1 manipulation; the genetic knockout was used in our study, whereas in the study reported by others, spadin was used to pharmacologically inhibit TREK-1 in cultured cortical neurons."
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"Direct inhibition of TREK-1 by spadin may also contribute to enhanced 5-HT neuron excitability."
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"Furthermore, spadin was unable to prevent activation of TREK-1 by BL-1249, CDC, or the related bioactive lipid, DHA."
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"Moreover, spadin blocks TREK-1 with higher affinity, IC 50 ~ 40-60 nM vs. IC 50 ~ 6 muM for the most used SSRI fluoxetine."
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"This hypothesis was validated by the discovery of spadin, that is a sortilin derived peptide and that specifically blocks TREK-1 channels [28], [30]."
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"Electrophysiological studies show that spadin efficiently blocks the TREK-1 activity in COS-7 cells, cultured pyramidal neurons, as well as CA3 hippocampal neurons in brain slices of wild-type mice and not in kcnk2 -/- mice, suggesting a specific effect of spadin on the TREK-1 channel."
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"Meanwhile, spadin reduces acid induced activity of TREK-1 and TREK-2 tandem heterodimeric channels [XREF_BIBR]."
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"Here, we showed that spadin blocked TREK-1 current exactly as it did for the transiently transfected TREK-1 channels (Figure 4A–C)."
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"In a previous study, pharmacological inhibition of TREK-1 by spadin increased the proportion of mature spines without affecting spine densities in cultured cortical neurons [24]."
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"Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices."
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"Recently, we demonstrated that TREK-1 channels are inhibited by spadin, a peptide that represents a new concept in antidepressant drug design [28]."
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