Dopaminergic neuron markers

A summary of the best dopaminergic neuron markers

​Dopaminergic neurons produce dopamine, a neurotransmitter with roles in neurological functions such as mood and reward. Progressive loss of dopaminergic neurons is the cause of many of the motor symptoms associated with Parkinson’s disease.

Tyrosine hydroxylase (TH)
An enzyme that converts L-tyrosine to L-3,4-dihydroxyphelylalanine (L-DOPA), which is a dopamine precursor.

Rat brain sections stained with anti-tyrosine hydroxylase (ab75875).

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​Tyrosine hydroxylase inhibitors and activators

ProductActivity
3-Iodo-L-tyrosine (MIT) (ab144773)Tyrosine hydroxylase inhibitor. Inhibits dopamine synthesis. Stimulates prolactin secretion.
​O,α-Dimethyl-DL-tyrosine (ab144755)
,α-Dimethyl-DL-tyrosine (ab144755)
Tyrosine hydroxylase inhibitor. Potential modulator of dopamine synthesis.
​​3-Iodo-L-tyrosine (MIT) (ab144773)​Tyrosine hydroxylase activator. Shows neuroprotective and cardioprotective effects in vivo.



Dopamine transporter (DAT)
A transmembrane transporter that controls the re-uptake of extracellular dopamine into presynaptic neurons.

Mouse substantia nigra sections stained with anti-dopamine transporter (ab128848).

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Dopamine transporter inhibitors

ProductActivity
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.



FOXA2
A transcriptional activator that regulates specification and differentiation of dopaminergic neurons.

Mouse substantia nigra sections stained with anti-FOXA2 (ab108422).

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GIRK2
A G-protein regulated potassium channel expressed within certain dopaminergic neurons of the substantia nigra.

​Mouse substantia nigra tissue sections stained with anti-GIRK2 (ab65096).

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GIRK2 inhibitors and activators

ProductActivity
ML297 (VU0456810) (ab143564)Potent, selective GIRK activator.
Ifenprodil hemitartrate (ab120111)Reversible inhibitor of GIRK activity.
Pimozide (ab142135)GIRK inhibitor at nanomolar concentration.



​Nurr1

A transcription factor that induces TH expression and subsequently dopaminergic neuron differentiation.

Rat cerebral nerve cells stained with anti-nurr1 (ab41917).

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LMX1B
A transcription factor involved in a number of processes during dopaminergic neuron development.

Human brain tissue stained with anti-LMX1B (ab139736).

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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).


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