Ace Therapeutics is committed to providing useful G protein-coupled receptor (GPCR) activation data for many tissues in mice to rationalize the use of animals to model GPCR function in psychiatric disorders and to help you identify new therapeutic targets for psychiatric disorders and predict targeted side effects. Our scientists have deep expertise in psychiatry, and our full-service and support programs can accelerate your psychiatric research and anti-psychotic drug development process.

Introduction of Functional GPCR Activation Assay in Psychiatry

The GPCR is the most common target of neuropharmacological drugs in the central nervous system (CNS). The GPCR is activated by a variety of neurotransmitters and their activation in turn causes slow synaptic transmission. The GPCR is closely associated with a variety of psychiatric disorders such as schizophrenia. In the brain, the striatum is strongly innervated by the ventral tegmental area (VTA), which plays a central role in the manifestation of psychiatric disorders. And recent studies in genetically engineered animal models and molecular biology suggest that certain striatal-rich GPCRs have the potential to be therapeutic psychiatric receptors.

Fig. 1 Striatal-enriched GPCRs in medium-sized spiny neurons (MSNs) in striatum. (Komatsu H., 2015)

Functional GPCR Activation Assay Services

Ace Therapeutics assays GPCR activation by measuring GTP binding. In this assay, we will measure the binding of a non-hydrolysable GTP analogue to a cell membrane containing an overexpressed target GPCR. When a GPCR is activated by an agonist, the receptor changes conformation to expose the binding site of the G protein complex. Once this G-protein complex is bound, the Gα protein can release GDP and bind GTP. since the GTP used in the assay is a radiolabeled non-hydrolyzable analogue (³⁵SγGTP), we will be able to measure the activation of the GPCR under study by measuring the amount of radiolabeled GTP bound to the cell membrane. If hydrolyzable GTP is used in the assay, the GTP will be hydrolyzed back to GDP by the GTPase activity (turnover) of the Gα protein, removing the radiolabeled γ-phosphate from the radiochemistry and leaving no radioisotope associated with the cell membrane for detection. .

Assay Formats

• SPA assays for GTP binding
• FlashPlate assays for GTP binding
• Filtration assays for GTP binding

Advantages of Our Approach

• Assays can usually be optimized in one day
• Larger volumes can be handled
• Fewer analytical development steps
• No washing steps can be achieved
• Low throughput (only a few assays) or high throughput

What Can We Help You Achieve in Psychiatry with GPCR Activation Assay?

• Providing a unified understanding of the underlying structural and functional mechanisms of GPCR activation
• Facilitating rational drug design for new therapies for neuropsychiatric disorders ranging from migraine to schizophrenia and depression
• Developing new drugs that target the GPCR signaling cascade
• Investigating the role of GPCR kinase interacting protein 1 (GIT1)
• Investigating the role of G proteins and GPCR-mediated signaling in the pathophysiology of psychiatric disorders
• Studying biased agonism in the mu-opioid receptor (MOR)

Ace Therapeutics offers functional GPCR activation assays for the study of various psychiatric disorders to help researchers identify biomarkers and unravel the pathogenesis of psychiatric disorders. Quantitative measurements of GPCR activation and inhibition of protein recruitment can be accurately determined using our assay system. Our method is well suited for HTS applications and is ideal for miniaturization. If you are interested in our services, please feel free to make an inquiry.

Reference

1. Komatsu H. Novel Therapeutic GPCRs for Psychiatric Disorders. Int J Mol Sci. 2015, 16(6):14109-14121.