|CSC-DC006518||Panoply™ Human GPR12 Knockdown Stable Cell Line||Inquriy|
|CSC-SC006518||Panoply™ Human GPR12 Over-expressing Stable Cell Line||Inquriy|
|CDCB185904||Rabbit GPR12 ORF clone (XM_008259883.1)||Inquriy|
|CDCL113831||Human Gpr12 ORF clone (NM_001010941.2)||Inquriy|
|CDCR244974||Mouse Gpr12 ORF Clone(NM_008151.3)||Inquriy|
|CDCR371549||Rat Gpr12 ORF Clone(NM_001037295.1)||Inquriy|
|CDCR379410||Rat Gpr12 ORF Clone(NM_030831.1)||Inquriy|
|CDFR004509||Rat Gpr12 cDNA Clone(NM_001037295.1)||Inquriy|
|CDFR012363||Rat Gpr12 cDNA Clone(NM_030831.1)||Inquriy|
|MiUTR1M-05282||GPR12 miRNA 3'UTR clone||Inquriy|
|MiUTR1M-05283||GPR12 miRNA 3'UTR clone||Inquriy|
|MiUTR1R-02208||GPR12 miRNA 3'UTR clone||Inquriy|
|MiUTR1R-02209||GPR12 miRNA 3'UTR clone||Inquriy|
|SHH097481||shRNA set against Mouse Gpr12(NM_001010941.2)||Inquriy|
|SHH097517||shRNA set against Mouse Gpr12(NM_008151.3)||Inquriy|
|SHH306158||shRNA set against Human GPR12 (NM_005288.3)||Inquriy|
|SHH306162||shRNA set against Mouse GPR12 (NM_008151.3)||Inquriy|
|SHH306166||shRNA set against Rat GPR12 (NM_030831.1)||Inquriy|
G protein-coupled receptor 12 (GPR12) belongs to the rhodopsin families of G protein-coupled receptors (GPCRs), which are crucial therapeutic targets. GPR12 was first cloned from a mouse cDNA library in 1993 and was originally named GPCR21. This was followed by cloning of human GPR12, along with the two related orphan receptors GPR3 and GPR6, from a human genomic DNA library. In the brain, GPR12 is located in the medial habenular nucleus, and to a lesser extent in cerebral cortex, hippocampus, striatum, and olfactory bulb. Peripherally GPR12 is found in the testis and oocytes. GPR12 is involved in several physiological processes. For instance, GPR12 plays an important role in meiotic arrest in rat oocytes. Furthermore, GPR12 participates in the process of neurite outgrowth and could contribute to brain development.
GPR12 and neurite outgrowth and neuronal development
The lab of Ignatov et al. showed that the lysophospholipid SPC is a high-affinity ligand for GPR12. In vitro cell culture suggested that embryonic cerebral cortical neurons had increased synaptic contacts following SPC treatment, and HT22 hippocampal cells exhibited increased cell proliferation and clustering in response to SPC. These results led the lab to conclude that by interacting with GPR12, SPC can positively influence the proliferation of neuronal precursor cells and the differentiation and maturation process of post-mitotic neurons. As with GPR3 and GPR6, Tanaka et al. revealed that GPR12 overexpression also increased neurite outgrowth. In fact, GPR12-mediated outgrowth was the most prominent of the three receptors. In experiments in which GPR3 was knocked down, GPR12 also rescued neurite outgrowth. However, similar to GPR6, GPR12 exhibits low expression in rat cerebellar granule neurons. In 2012, Lu et al. showed that GPR12 induces neurite outgrowth in PC12 cells. The authors demonstrated that GPR12 overexpression instigated the differentiation of PC12 cells into neuron-like cells with the increased size of the cell and neurite generation. The researchers proposed that a possible mechanism for this phenotype is the activation of ERK1/2 signaling and a substantial increase in the expression of multiple genes related to neurite outgrowth.
GPR12 and obesity and metabolic disorders
Bjursell et al. investigated the importance of GPR12 in metabolism. They found that food intake was not significantly affected in GPR12 knockout mice compared to wild-type mice. However, the GPR12 knockout mice exhibited increased body weight and body fat mass, decreased respiratory exchange ratio, dyslipidemia, and hepatic steatosis. The authors concluded that GPR12 plays an important role in energy balance, which is supported by the fact that GPR12 knockout mice developed obesity and decreased energy expenditure.
A novel molecular target for Cannabidiol
In spite of being orphans, GPR12 share about 35% amino acid sequence identity in the transmembrane regions with the CB1 and CB2 cannabinoid receptors. Thus, it is considered a “cannabinoid receptor-like orphan GPCR”. The research has shown that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, played as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Therefore, GPR12 is a novel molecular target for CBD. The structure-activity relationship studies of CBD indicate that both the free hydroxyl and the pentyl side chain are critical for the effects of CBD on GPR12. In addition, studies using cholera toxin, which blocks Gs protein and pertussis toxin, which blocks Gi protein, revealed that Gs, but not Gi is involved in the inverse agonism of CBD on GPR12. CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter the viscoelasticity of metastatic cancer cells. Since these studies have shown that CBD is an inverse agonist for GPR12, this provides a novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.
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