Dopamine Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs' membrane preparations are useful for membrane protein research. We offer membrane preparations to study the role of membrane proteins in diseases. Membrane preparations from Creative Biolabs are quality-assured frozen membranes from cells expressing recombinant or natural receptors.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
The most prevalent catecholamine in the brain is dopamine (DA). It is generally recognized that DA plays a crucial role in the central nervous system's (CNS) control of a variety of physiological processes. Parkinson's disease, Tourette's syndrome, schizophrenia, attention deficit hyperactivity disorder (ADHD), and the development of pituitary tumors have all been connected to dopaminergic system dysregulation.
Creative Biolabs can provide a wide variety of dopamine family related assays and products to meet the needs of drug discovery:
Overview of Dopamine Family
Dopamine is an adrenergic substance that acts on receptors D1 to D5 to produce a variety of different effects. The D1-like family (D1, D4) and the D2-like family are two groups that make up the receptors (D2, D3, D5). Neurotransmitter dopamine is produced in the hypothalamus, substantia nigra, pars compacta, and ventral tegmental area (VTA). Axons from these regions travel to different regions of the brain along four main pathways.
- D1-like family
D1-like receptors bind to Gαs/olf and increase adenylate cyclase activity, which in turn triggers the activation of PKA and other signaling molecules. Although Gαolf appears to promote adenylate cyclase activity and is highly expressed in dopaminergic regions like the neostriatum, Gαs also appears to mediate D1-like receptor activation. Moreover, D1-like receptors can either directly or indirectly mediate signaling at a number of voltage-gated ion channels, in addition to NMDA and GABAA receptors, by acting on DARPP-32, the MAPK pathway, and other kinases and phosphatases.
Fig.1 The implications of functional selectivity. (Boyd & Mailman, 2012)
- D2-like family
The Gαi/o class of G proteins, which are deactivated by pertussis toxin-catalyzed ADP-ribosylation, are a key modulator of D2-like signaling. Adenylate cyclase and cAMP buildup are inhibited by G proteins of the Gαi/o class. In most clonal and in situ cells, adenylate cyclase is inhibited by both D2 and D4 receptors. Compared to other D2-like receptors, D3 dopamine receptors have a tendency to bind agonists with a higher affinity. Additionally, it has been proposed that the GTP-insensitive way in which D3 dopamine receptors bind agonists is due to a receptor conformation that has a high affinity for agonists regardless of interactions with G proteins.
Fig.2 Scheme of the putative structure of the D2R receptor isoforms. (Vallone, 2000)
Dopamine Family Drug Discovery
Although the positive symptoms of schizophrenia are often well-managed by current APDs, unwelcome side effects and a lack of efficacy in managing the negative and cognitive symptoms have brought attention to the need for new and enhanced APDs. The hunt for functionally selective drugs should also look at other signaling pathways that the D1 and D2 receptors stimulate. The dopamine receptor system is the main target for APDs, but pinpointing the dopamine-mediated signaling pathways responsible for the unique symptoms of schizophrenia will aid in concentrating drug discovery and development efforts.
References
- Boyd, K. N., & Mailman, R. B. Dopamine receptor signaling and current and future antipsychotic drugs. Current antipsychotics. 2012, 53-86.
- Vallone, D.; et al. Structure and function of dopamine receptors. Neuroscience & biobehavioral reviews. 2000, 24(1): 125-132.
