Perspective ARTICLE

Front. Syst. Neurosci., 30 June 2011 | http://dx.doi.org/10.3389/fnsys.2011.00055

Nitric oxide–soluble guanylyl cyclase–cyclic GMP signaling in the striatum: new targets for the treatment of Parkinson’s disease?

  • 1 Department of Neuroscience, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
  • 2 Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

Striatal nitric oxide (NO)-producing interneurons play an important role in the regulation of corticostriatal synaptic transmission and motor behavior. Striatal NO synthesis is driven by concurrent activation of NMDA and dopamine (DA) D1 receptors. NO diffuses into the dendrites of medium-sized spiny neurons which contain high levels of NO receptors called soluble guanylyl cyclases (sGC). NO-mediated activation of sGC leads to the synthesis of the second messenger cGMP. In the intact striatum, transient elevations in intracellular cGMP primarily act to increase neuronal excitability and to facilitate glutamatergic corticostriatal transmission. NO–cGMP signaling also functionally opposes the inhibitory effects of DA D2 receptor activation on corticostriatal transmission. Not surprisingly, abnormal striatal NO–sGC–cGMP signaling becomes apparent following striatal DA depletion, an alteration thought to contribute to pathophysiological changes observed in basal ganglia circuits in Parkinson’s disease (PD). Here, we discuss recent developments in the field which have shed light on the role of NO–sGC–cGMP signaling pathways in basal ganglia dysfunction and motor symptoms associated with PD and L-DOPA-induced dyskinesias.

Keywords: basal ganglia, striatum, dopamine, nitric oxide, Parkinson’s disease

Citation: West AR and Tseng KY (2011) Nitric oxide–soluble guanylyl cyclase–cyclic GMP signaling in the striatum: new targets for the treatment of Parkinson’s disease?. Front. Syst. Neurosci. 5:55. doi: 10.3389/fnsys.2011.00055

Received: 24 December 2010; Paper pending published: 27 March 2011;
Accepted: 16 June 2011; Published online: 30 June 2011.

Edited by:

Elizabeth Abercrombie, Rutgers-Newark: The State University of New Jersey, USA

Reviewed by:

Dalton J. Surmeier, Northwestern University, USA
Alessandro Stefani, University of Rome, Italy
M. Gustavo Murer, Universidad de Buenos Aires, Argentina

Copyright: © 2011 West and Tseng. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Anthony R. West, Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. e-mail: Anthony.West@rosalindfranklin.edu; Kuei Y. Tseng, Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA. e-mail: kuei-yuan.tseng@rosalindfranklin.edu