Neurotransmitter Transporter Drug Discovery Assays
Background
Neurotransmitter transporters are responsible for transporting neurotransmitters across these membranes and then routing them to specific intracellular locations. Neurotransmitter transporters use electrochemical gradients that arise across cell membranes to accomplish their goals. Because uptake systems are frequently selective and connected with a specific neurotransmitter, such neurotransporter cotransport systems are exceedingly diverse, according to current research.
Subtypes and Mechanism
Creative Biolabs offers neurotransmitter transporter drug discovery assays, including dopamine transporter, norepinephrine transporter, serotonin transporter, vesicular monoamine transporter, adenosine transporters, nucleoside transporter and etc.
| Subtype | Mechanism | Pharmacology |
| Serotonin Transporter (SERT) | SERT restores serotonin to synaptic boutons by removing it from the synaptic cleft. It blocks serotonin's effects while allowing it to be reused by the presynaptic cell. | SERT is important sites for agents that treat psychiatric disorders. |
| Norepinephrine Transporter (NET) | NET transports norepinephrine released synaptically back into the presynaptic neuron. NET will accept up to 90% of the norepinephrine produced in the cell. | Inhibition of NET has therapeutic applications in the treatment of ADHD, substance abuse, neurodegenerative disorders and clinical depression. |
| Dopamine Transporter (DAT) | DAT is a symporter that transports dopamine across the cell membrane by linking it to the energetically advantageous flow of sodium ions into the cell from high to low concentration. | DAT is the target of substrates, dopamine releasers, transport inhibitors and allosteric modulators. |
| Nucleoside Transporter (ENT) | ENTs are critical for nucleotide synthesis in cells lacking de novo nucleoside synthesis routes, as well as the uptake of cytotoxic nucleosides employed in cancer and viral chemotherapies. | Mutations in ENT have been associated with H syndrome, pigmented hypertrichosis with insulin dependent diabetes and Faisalabad histiocytosis. |
Published Data
| Paper Title | Serotonin transporter–ibogaine complexes illuminate mechanisms of inhibition and transport |
| Journal | Nature |
| Published | 2019 |
| Abstract | By recycling serotonin into presynaptic neurons in a sodium- and chloride-dependent manner, the serotonin transporter (SERT) controls neurotransmitter homeostasis. Selected serotonin reuptake inhibitors are used to treat severe depression and anxiety disorders. They looked examined SERT's complexes with ibogaine, a hallucinogenic natural substance having psychotropic and anti-addictive characteristics, to understand structure-based processes for transport. |
| Result |
They identified the inhibition of serotonin absorption by ibogaine for the SERT variations in order to examine the regulation of SERT by ibogaine. a, Chemical structures of ibogaine and serotonin. b, Plots of [14C]5-HT uptake for ts2-active SERT. c, Plots of [3H]ibogaine saturation binding to ts2-active SERT . d, In the presence of 100 mM KCl or 100 mM NaCl, 10 M MTSACMA was used to label the S277C mutant for 10 minutes.
|
Fig.1. Ibogaine binding, uptake and labelling experiments. (Coleman, 2019)
Reference
- Coleman, J. A.; et al. Serotonin transporter–ibogaine complexes illuminate mechanisms of inhibition and transport. Nature. 2019, 569(7754): 141-145.
