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Overview
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The Cholinergic Receptor, Muscarinic 4 (CHRM4), also known as the Muscarinic Acetylcholine Receptor M4, is a subtype of the muscarinic acetylcholine receptors, which are G protein-coupled receptors (GPCRs). These receptors are activated by the neurotransmitter acetylcholine and play a key role in the parasympathetic nervous system. The M4 receptor is primarily coupled with the Gi/Go class of G proteins, leading to the inhibition of adenylate cyclase, which reduces cyclic AMP (cAMP) levels within the cell. This signaling cascade influences various physiological processes, including modulation of neurotransmitter release and regulation of neuronal excitability. CHRM4 is predominantly expressed in the central nervous system, particularly in areas such as the striatum, where it is involved in modulating dopaminergic activity. This receptor plays a significant role in motor control, cognitive functions, and the regulation of emotional responses. Due to its involvement in these critical pathways, CHRM4 is a target of interest for the treatment of several neurological and psychiatric disorders, including schizophrenia, Parkinson's disease, and drug addiction. Research continues to investigate the therapeutic potential of targeting CHRM4 in order to develop treatments for these conditions, focusing on its ability to modulate dopaminergic and cholinergic signaling in the brain.
This kit uses AAV vectors with a CMV promoter to co-express the CHRM4 and cyclic nucleotide-gated (CNG) channel, allowing researchers to conduct high-throughput screening and functional analysis of potential CHRM4 -targeting compounds. The kit provides a sensitive and reliable method for evaluating the pharmacological properties of CHRM4 drugs, such as agonists and antagonists, in a live-cell environment.Please contact us at for specific academic pricing.
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.
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Overview