AAV ACTOne Gi-GPCR Assay Kit-ORL1

Opioid Receptor-Like 1 (OPRL1), also known as the Nociceptin/Orphanin FQ Receptor (NOP receptor), is a G protein-coupled receptor (GPCR) that is structurally similar to the classical opioid receptors (mu, delta, and kappa) but has distinct pharmacological properties. The endogenous ligand for OPRL1 is nociceptin, also known as orphanin FQ, a peptide that shares structural similarities with the opioid peptides but does not produce the traditional opioid effects such as euphoria or strong analgesia. When activated by nociceptin, OPRL1 primarily couples with the Gi/Go class of G proteins, leading to inhibition of adenylate cyclase, a reduction in cyclic AMP (cAMP) levels, and modulation of ion channels. This signaling cascade results in a variety of physiological effects, including modulation of pain, stress response, mood, and behavior. OPRL1 is widely expressed in the central nervous system, particularly in regions involved in pain processing, such as the spinal cord, brainstem, and limbic system, as well as in peripheral tissues. Activation of OPRL1 by nociceptin can produce both anti-nociceptive (pain-blocking) and pro-nociceptive (pain-enhancing) effects, depending on the context and location of activation. Unlike classical opioid receptors, OPRL1 activation does not lead to significant respiratory depression, making it an attractive target for developing new analgesics. In addition to its role in pain modulation, OPRL1 is involved in regulating a range of other functions, including stress, anxiety, feeding behavior, and addiction. The receptor is a target of interest for the development of novel therapeutics for conditions such as anxiety, depression, and substance use disorders, as well as for non-opioid pain relief. Research into OPRL1 continues to explore its unique pharmacology and potential as a therapeutic target for a variety of clinical applications.
This kit uses AAV vectors with a CMV promoter to co-express the ORL1 and cyclic nucleotide-gated (CNG) channel, allowing researchers to conduct high-throughput screening and functional analysis of potential ORL1-targeting compounds. The kit provides a sensitive and reliable method for evaluating the pharmacological properties of ORL1 drugs, such as agonists and antagonists, in a live-cell environment.

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Background

ACTOne™ is the only high-throughput GPCR screening technology that can directly measure the intracellular changes of the secondary messenger cyclic AMP (cAMP) in living cells, in real-time. It uses a proprietary modified cyclic nucleotide-gated (CNG) channel, which is co-localized with adenylate cyclase at the plasma membrane, as a biosensor of cAMP activity. The CNG channel opens when the cAMP level near the plasma membrane increases, resulting in ion flux and cell membrane depolarization. The influx of cations through the CNG channel can be quantified using fluorescent ion indicators or membrane potential (MP) dyes. It provides information on real time intracellular cAMP changes and is highly sensitive. By combining kinetic and endpoint readouts, we are able to capture and analyze transient responses from endogenous GPCRs and weak responses caused by weak Gs or Gi coupled GPCR activities. Using ACTOne, we are able to detect the subcellular cAMP concentration changes directly caused by GPCR activation. Real-time kinetic readouts minimize artifacts, and provide greater content and more statistically relevant data. The intensity of signal increase caused by GPCR activation is directly related to the receptor number on cell surface. Using ACTOne assay, we were able to detect activities of some endogenous Gs coupled receptors in HEK293 cells that have not been reported in literature. In addition, we have also detected weak Gs coupled activity of a GPCR that was widely considered to be only linked to Gq coupled pathway. The ACTOne assay also provides a useful tool for GPCR de-orphanization.