mProX™ Human OPRK1 Stable Cell Line

Goodman RL, et al. "Lesions of KNDy and Kiss1R neurons in the arcuate nucleus produce different ." Endocrinology, 2023.
The current model for the synchronization of GnRH neural activity driving GnRH and LH pulses suggests that a set of arcuate (ARC) neurons containing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) act as the GnRH pulse generator. This study examined the functional role of ovine KNDy neurons and the nearby Kiss1 receptor (Kiss1R)-containing cells through lesions produced with saporin (SAP) conjugates. The findings showed that NK3-SAP injection eliminated over 90% of KNDy cells, while Kiss-SAP lesioned about two-thirds of the Kiss1R population without affecting KNDy or GnRH cell number. Both lesions resulted in a considerable decrease in LH pulse amplitude, but had different effects on LH pulse patterns. NK3-SAP increased the inter-pulse interval (IPI), while Kiss-SAP had no effect. However, Kiss-SAP disrupted the regular hourly occurrence of LH pulses, while NK3-SAP did not. Since Kiss1R is not expressed in KNDy cells, the co-localization of eight neurotransmitters and three receptors in ARC Kiss1R-containing cells was assessed using HiPlex RNAScope. The results showed that Kiss1R cells primarily contained markers for GABA (68%), glutamate (28%), ESR1 (estrogen receptor-alpha) mRNA, and OPRK1 (kappa opioid receptor) mRNA. These findings support the notion that KNDy neurons play an essential role in GnRH pulses in ewes, while ARC Kiss1R cells do not, but they do maintain the amplitude and regularity of GnRH pulses. It is thus suggested that ARC Kiss1R neurons in sheep form a positive feedback circuit that reinforces the activity of the KNDy neural network, with GABA or glutamate being most likely involved.
Pubmed: 37776515   DOI: 10.1210/endocr/bqad148

Yu J, et al. "Methylation and expression quantitative trait loci rs1799971 in the OPRM1 gene ." Neuroscience letters, 2023.
The current study aimed to investigate the role of DNA methylation and genetic variants in opioid use disorder (OUD), a chronic and relapsing brain disease with significant mortality worldwide. Through analyzing 111 healthy controls (HCs) and 120 OUD patients, the DNA methylation levels in the promoter region of the OPRM1, OPRD1, and OPRK1 genes were examined. Additionally, the relationships between three tag single nucleotide polymorphisms (SNPs) and the methylation levels and expression levels of these genes were explored. Furthermore, the associations between SNPs and susceptibility to and characteristics of OUD were determined in a larger group of 930 HCs and 801 patients with OUD. The results showed that two SNPs (rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene) were both methylation quantitative trait loci (mQTLs) and expression quantitative trait loci (eQTLs). Moreover, unique correlations were observed between mQTLs and methylation levels of certain CpG sites in the OUD group compared to the HC group. Surprisingly, both of the identified mQTLs and eQTLs were associated with susceptibility to OUD. These findings suggest that mQTLs and eQTLs in these genes may be potential biomarkers for better management of opioid misuse, providing insight into the mechanisms underlying genetic risk factors for OUD.
Pubmed: 37660978   DOI: 10.1016/j.neulet.2023.137468