Dopaminergic neuron markers
Related
A summary of the best dopaminergic neuron markers for your research
- Introduction
- Tyrosine hydrolase (TH)
- Dopamine transporter (DAT)
- GIRK2
- Transcription factors: NURR1, LMX1B, FOXA2
- Vesicular monoamine transporter: VMAT1 and VMAT2
- Fluorescent false neurotransmitters (FFNs)
Introduction
Dopaminergic neurons produce dopamine, a monoamine neurotransmitter with roles in neurological functions such as mood and reward.
The progressive loss of dopaminergic neurons is the cause of many of the motor symptoms associated with Parkinson’s disease. A widely used treatment for Parkinson's disease is Levodopa, which is a pure form of the precursor to dopamine, L-DOPA.
There are several well-characterized dopamine markers that can aid your research.
Tyrosine hydroxylase (TH)
Tyrosine hydroxylase (TH)
An enzyme that converts L-tyrosine to L-3,4-dihydroxyphelylalanine (L-DOPA), which is a dopamine precursor.
Image: Rat brain sections stained with anti-tyrosine hydroxylase (ab75875).
Browse all tyrosine hydroxylase antibodies
Tyrosine hydroxylase inhibitors
| Product | Activity |
| 3-Iodo-L-tyrosine (MIT) (ab144773) | Tyrosine hydroxylase inhibitor. Inhibits dopamine synthesis. Stimulates prolactin secretion. |
Dopamine transporter (DAT)
A transmembrane transporter that controls the re-uptake of extracellular dopamine into presynaptic neurons and pumps dopamine out of the synapse into the cytosol.
DAT is vital in maintaining sufficient dopamine levels in the neuron for release.
Image: Mouse substantia nigra sections stained with anti-dopamine transporter (ab128848).
Browse all dopamine transporter antibodies
Dopamine transporter inhibitors
| Product | Activity |
| Clomipramine hydrochloride (ab143213) | Selective α1-adrenoceptor antagonist. DAT blocker. |
| Benztropine mesylate (ab143332) | Potent DAT inhibitor. Selective M1 receptor antagonist. |
| Bupropion hydrochloride (ab120534) | Non-selective dopamine and norepinephrine transporter (DAT/NET) inhibitor. |
| GBR 12909 dihydrochloride (ab120607) | Potent, selective dopamine reuptake inhibitor. |
GIRK2
A G-protein regulated potassium channel expressed within certain dopaminergic neurons of the substantia nigra.
Image: Mouse substantia nigra tissue sections stained with anti-GIRK2 (ab65096).
GIRK2 inhibitors and activators
| Product | Activity |
| ML297 (VU0456810) (ab143564) | Potent, selective GIRK activator. |
| Ifenprodil hemitartrate (ab120111) | Reversible inhibitor of GIRK activity. |
| Pimozide (ab142135) | GIRK inhibitor at nanomolar concentration. |
NIRR2
A transcription factor that induces TH expression and subsequently dopaminergic neuron differentiation.
Image: Rat cerebral nerve cells stained with anti-nurr1 (ab41917).
LMX1B
A transcription factor involved in a number of processes during dopaminergic neuron development.
Image: Human brain tissue stained with anti-LMX1B (ab139736).
FOXA2
A transcriptional activator that regulates specification and differentiation of dopaminergic neurons.
Mouse substantia nigra sections stained with anti-FOXA2 (ab108422).
Vesicular monoamine transporter: VMAT1 and VMAT2
During synaptic transmission, the vesicular monoamine transporter (VMAT) accumulates neurotransmitters in synaptic vesicles. There are two isoforms of this vesicular membrane protein; VMAT2 and VMAT 1.
VMAT1
VMAT1 accumulates monoamines in chromaffin cells of the adrenal medulla.
VMAT2
VMAT2 translocates monoamines such as the neurotransmitter dopamine from the cytosol into synaptic vesicles.
Fluorescent false neurotransmitters (FFNs)
Fluorescent false neurotransmitters (FFNs) are probes that act as novel optical tracers allowing imaging of neurotransmitter release from individual presynaptic terminals in the brain. They are designed to loosely mimic the overall topology and physical properties of monoamine neurotransmitters and have been engineered to have fluorescence properties.
FFNs have the capability for increasing the understanding of both fundamental and applied neurobiological research including research into neurodegeneration and drug addiction.
Advantages of using fluorescent false neurotransmitters:
- Optically study various aspects of synaptic transmission
- Compatible with GFP tags, including Alexa Fluor 488
- Photostable
- Suitable for standard fluorescent microscopy and two-photon fluorescence microscopy
Applications for FFN102, FFN202, and FFN511:
- Measure localization and activity of dopaminergic presynaptic terminals.
- Measure pH of secretory vesicles
- Visualize dopamine release from individual presynaptic terminals
FFN102 (Mini102)
- Rodent DAT and VMAT2 substrate. Enables two-photon microscopic imaging of localization and activity of dopaminergic presynaptic terminals in the striatum of mouse acute brain slice.
- More selective for dopaminergic synapses than FFN511.
- Exhibits greater fluorescence emission in neutral than acidic environments allowing optical measurement of synaptic vesicle content release.
FFN202 (Mini202)
- Rodent VMAT1 and VMAT2 substrate.
- Enables in situ pH measurement of secretory catecholamine vesicles in PC-12 cells.
FFN511
- A fluorescent probe for optical imaging and measurement of synaptic activity in the brain.
- Substrate for the synaptic vesicle monoamine transporter (VMAT2).
- FFN511 fluoresces sufficiently to provide resolution at the individual synaptic level but at concentrations that do not interfere with normal synaptic function. Inhibits 5HT binding to VMAT2 with an IC50 of 1 μM (comparable to dopamine itself).
References
- Austin, L. S. et al. Dopamine blocking activity of clomipramine in patients with obsessive-compulsive disorder. Biol. Psychiatry 30, 225–32 (1991).
- Hall, F. S. et al. Decreased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) function in knockout mice affects aging of dopaminergic systems. Neuropharmacology 76 Pt A, 146–55 (2014).
- Hartfield, E. M. et al. Physiological characterisation of human iPS-derived dopaminergic neurons. PLoS One 9, (2014).
- Jankovic, J., Chen, S. & Le, W. D. The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog. Neurobiol. 77, 128–138 (2005).
- Kaufmann, K. et al. ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice. ACS Chem. Neurosci. 4, 1278–86 (2013).
- Kobayashi, T., Washiyama, K. & Ikeda, K. Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil. Neuropsychopharmacology 31, 516–24 (2006).
- Kobayashi, T., Ikeda, K. & Kumanishi, T. Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. Br. J. Pharmacol. 129, 1716–22 (2000).
- Luo, F.-C. et al. Protective effect of panaxatriol saponins extracted from Panax notoginseng against MPTP-induced neurotoxicity in vivo. J. Ethnopharmacol. 133, 448–53 (2011).
- Nakatani, T., Kumai, M., Mizuhara, E., Minaki, Y. & Ono, Y. Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of dopaminergic neurons and control of floor plate cell differentiation in the developing mesencephalon. Dev. Biol. 339, 101–113 (2010).
- Ness, D. K., Foley, G. L., Villar, D. & Hansen, L. G. Effects of 3-iodo-L-tyrosine, a tyrosine hydroxylase inhibitor, on eye pigmentation and biogenic amines in the planarian, Dugesia dorotocephala. Fundam. Appl. Toxicol. 30, 153–61 (1996).
- Reyes, S. et al. GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area. J. Comp. Neurol. 520, 2591–607 (2012).
- Rothman, R. B., Baumann, M. H., Prisinzano, T. E. & Newman, A. H. Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction. Biochem. Pharmacol. 75, 2–16 (2008).
- Smythe, G. A. & Bradshaw, J. E. Different acute effects of the tyrosine hydroxylase inhibitors alpha-methyl-p-tyrosine and 3-iodo-L-tyrosine on hypothalamic noradrenaline activity and adrenocorticotrophin release in the rat. Aust. J. Biol. Sci. 36, 519–23 (1983).
- Stahl, S. M. et al. A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor. Prim. Care Companion J. Clin. Psychiatry 6, 159–166 (2004).
- Tanda, G. et al. Relations between stimulation of mesolimbic dopamine and place conditioning in rats produced by cocaine or drugs that are tolerant to dopamine transporter conformational change. Psychopharmacology (Berl). 229, 307–21 (2013).