A largely described SNP for the human NPSR gene is an Asn-Ile exchange at position 107 of the mature hNPSR protein (SNP591694 A>T; refSNP ID: rs324981). This receptor polymorphism seems to have functional implications since the hNPSRIle107 receptor displayed similar binding affinity but higher NPS potency (by approx. 10-fold) than hNPSRAsn107 (Reinscheid et al. 2005). This result has been replicated in different laboratories, using different assays (intracellular calcium and cAMP accumulation) as well as different cell types (HEK293 and CHO, Reinscheid et al. 2005, Bernier et al 2006, Camarda et al. 2013). Interestingly, this SNP has been reported to be associated with with panic disorder (Okamura et al. 2007, Raczka et al. 2010, Donner et al. 2010, Domschke et al. 2011) , sleep behaviour (Gottlieb et al. 2007), obsessive-compulsive disorders (Lennertz et al. 2013), hyperactivity and impulsivity (Laas et al. 2013) bowel disease (D'Amato et al. 2007) and asthma susceptibility (Bernier et al 2006).
Considering all this, it would be useful to know wich isoform of the human NPSR (Asn107 or Ile107) has been used in the present research article to evaluate the NPS and L6-NPS activity in the CRE-luciferase assay and in the NFAT luciferase assay. Moreover, it would be of high interest to study the activity of L6-NPS at both the hNPSRIle107 and the hNPSRAsn107 receptor isoform and compare it with those of NPS.