Cell Line

Parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR1) is a G protein coupled receptor which mediates the actions of both amino-terminal PTH and PTHrP fragments. The most abundant expression of PTHR1 is found in renal tubular cells and in osteoblasts, where the PTH/PTHrP receptor mediates the endocrine actions of PTH, and in prehypertrophic chondrocytes of the metaphyseal growth plate, where it mediates the autocrine/paracrine actions of PTHrP. Intact PTH (PTH 1-84) is compounded by a peptide of 84 amino acids (AA), the amino-terminal sequence, constituted by the first 34 AA (N-terminal structure), is necessary for its action.

Hypocretin (orexin) receptor 2, also known as OX2, is a human protein encoded by the HCRTR2 gene. Orexin A and orexin B are neuropeptides originally identified as endogenous ligands for OX2. Orexin neuropeptides are produced by a small group of neurons in the lateral hypothalamic and perifornical areas, a region that is classically implicated with the control of mammalian feeding behavior. Orexin neurons that project throughout the central nervous system to nuclei are known to be important in the control of feeding, sleep-wakefulness, neuroendocrine homeostasis, and autonomic regulation.

5-Hydroxytryptamine (5-HT, also commonly known as serotonin) is synthesized in enterochromaffin cells in the intestine and in serotonergic nerve terminals. In the periphery, 5-HT mediates gastrointestinal motility, platelet aggregation, and contraction of blood vessels. Many functions of the central nervous system are influenced by 5-HT, including sleep, motor activity, sensory perception, arousal, and appetite. A family of 12 GPCRs and one ion channel mediate the biological effects of 5-HT (Hoyer et al., 1994). 5HT2C is expressed in the brain and spinal cord, especially the choroid plexus. 5HT2C receptor agonists may have important clinical value in the treatment of mental and eating disorders, such as depression, panic anxiety, OCD, bulimia, and obesity. GenScript's cloned human 5-HT2C expressing cell line is generated in the CHO-K1 host.

Numerous studies have demonstrated that the calcitonin receptor (CALCR) is a specific marker of osteoclast differentiation and that calcitonin can inhibit bone resorption in vitro and in vivo. Mice lacking calcitonin and calcitonin gene-related peptide (CGRP) have a high bone mass phenotype due to an increase in bone formation parameters. Expression of calcitonin (CT) and its receptor (CTR) generate survival, adhesion, pro-inflammatory, and pro-metastatic pathways. Moreover, data indicate a pivotal role for CT-CTR axis in advanced prostate cancer PC metastasis and may serve as a potential therapeutic target for advanced PC.

GPR103 is known as an orphan G protein-coupled receptor with reported expression in brain, heart, kidney, adrenal gland, retina, and testis. GPR103 mRNA has been reported to be highly expressed in the superficial layers of the entire spinal cord and a high density of 26RFa binding sites was observed in the superficial layers of the dorsal horn. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Therefore, the current experiments investigated the effects of QRFP administration in rats and the effects of a high fat diet on prepro-QRFP mRNA and GPR103 receptor mRNA levels. 26RFa and QRFP are endogenous ligands of GPR103. An immunohistochemical study revealed that GPR103-like immunoreactivity (LI) was observed in the superficial layers of spinal dorsal horn, that QRFP-LI was observed in the dorsal root ganglion and that intrathecal 26RFa suppressed the expression of Fos-LI induced by paw formalin injection in

Dopamine is the predominant catecholamine neurotransmitter found in mammalian brain, where it controls a variety of functions including locomotor activity, cognition, emotion, positive reinforcement, food intake, and endocrine regulation. It also plays multiple roles in the periphery as a modulator of cardiovascular function, catecholamine release, hormone secretion, vascular tone, renal function, and gastrointestinal motility. The dopamine receptor family consists of five members, which are classified into two groups, D1-like (D1 and D5) and D2-like (D2, D3, and D4). D5 receptor has a 10-fold higher affinity for dopamine than the D1 receptor.

Opioid receptor family includes three classic receptors, μ, δ, and κ, also known as OP1, OP2 and OP3, respectively. The receptors are G_i/o-coupled GPCRs which will reduce intracellular cAMP levels after activation. δ-opioid receptor modulates many kinase cascades including ERKs, Akts, JNKs, STAT3, P38 involving Src, Ras, Rac, Raf-1, Cdc42, RTKs. In addition, δ-opioid receptor has also been proposed to interact with μ receptors. The observed pharmacological cross-talk may partially arise from agonist cross-reactivity.

A1 is a receptor for adenosine. It is demonstrated that the A1 receptor is ubiquitous throughout the entire body. Activation of A1 elicits an inhibition of adenylate cyclase and therefore a decrease in the cAMP concentration. A1 receptors are implicated in sleep promotion by inhibiting wake promoting cholinergic neurons in the basal forebrain. Adenosine antagonists are widely used in neonatal medicine.

Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biologic effects of somatostatin are probably mediated by a family of G protein-coupled receptors that are expressed in a tissue-specific manner. SST2 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in cerebrum and kidney. Studies showed the involvement of the SST2 receptor in the inhibition of glucagon secretion.