Year-end Sale % OFF 
Abstract
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.
Highlights
Work by Schmidt and colleagues showed that the facilitatory effects of D1-like receptor agonist and D2 receptor antagonist on striatal tissue levels of cGMP are abolished in neuronal NOS (nNOS)−/− mice (Siuciak et al, 2006)
Studies reported to date indicate that it will be important to clarify how nitric oxide (NO)–soluble guanylyl cyclases (sGC)–cGMP signaling is dysregulated in hypo- and hyperdopaminergic states and how this can be normalized to restore function within striatal output pathways
The above studies indicate that cGMP synthesis and catabolism, as well as the temporal and spatial patterning of NO–sGC–cGMP signaling may be perturbed in medium-sized spiny neurons (MSNs) in the parkinsonian striatum
Summary
Nitric oxide–soluble guanylyl cyclase–cyclic GMP signaling in the striatum: new targets for the treatment of Parkinson’s disease?. In the same study these authors reported that the D2 receptor antagonists haloperidol and sulpiride robustly elevated striatal tissue levels of cGMP. These findings have been confirmed and extended in more recent studies (Di Stefano et al, 2005; Siuciak et al, 2006). Work by Schmidt and colleagues showed that the facilitatory effects of D1-like receptor agonist and D2 receptor antagonist on striatal tissue levels of cGMP are abolished in nNOS−/− (i.e., knockout) mice (Siuciak et al, 2006). The above studies confirm that both D1- and D2-like receptor activation strongly regulates
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
