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In addition to mGPR17, several naturally occurring hGPR17L variants have distinct downstream second messenger signaling profiles when expressed in HEK293 cells [26]: human GPR17L-V96M has similar agonist-mediated inhibition of cAMP to that of hGPR17L-WT, but without the reversal of inhibition typically observed upon treatment with greater than 1 µM MDL29,951 [26], and GPR17L-V96M shows impaired agonist-mediated calcium mobilization and β-arrestin recruitment [26]
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