QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 4, 2004, 24(31):7007-7014; doi:10.1523/JNEUROSCI.0676-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Corvol, J.-C. Articles by Hervé, D. Search for Related Content PubMed PubMed Citation Articles by Corvol, J.-C. Articles by Hervé, D.

 Previous Article  |  Next Article 

Neurobiology of Disease
Persistent Increase in Olfactory Type G-Protein Subunit Levels May Underlie D₁ Receptor Functional Hypersensitivity in Parkinson Disease

Jean-Christophe Corvol,¹ Marie-Paule Muriel,² Emmanuel Valjent,¹ Jean Féger,² Naïma Hanoun,³ Jean-Antoine Girault,¹ Etienne C. Hirsch,² and Denis Hervé¹

¹Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie Unité 536, Institut du Fer à Moulin, 75005 Paris, France, ²INSERM Unité 289, Centre Hospitalier Universitaire Pitié-Salpétrière, 75013 Paris, France, and ³INSERM Unité 288, Fac Médecine Pitié-Salpétrière, 75013 Paris, France

Although L-dopa remains the most effective treatment of Parkinson disease, its long-term administration is hampered by the appearance of dyskinesia. Hypersensitivity of dopamine D₁ receptors in the striatum has been suggested to contribute to the genesis of these delayed adverse effects. However, D₁ receptor amounts are unchanged in Parkinson disease, suggesting alterations of downstream effectors. In rodents, striatal D₁ receptors activate adenylyl cyclase through olfactory type G-protein subunit (Golf) and G-protein 7 subunit (G7). We found that Golf was enriched in human basal ganglia and was markedly diminished in the putamen of patients with Huntington disease, in relation with the degeneration of medium spiny neurons. In contrast, in the putamen of patients with Parkinson disease, Golf and G7 levels were both significantly increased. In the rat, the degeneration of dopamine neurons augmented Golf levels in the striatal neurons, specifically at the plasma membrane, an effect accounting for the increase of D₁ response on cAMP production in dopamine-depleted striatum. In lesioned rats, Golf levels were normalized by a 3 week treatment with L-dopa or a D₁ agonist but not with aD₂-D₃ agonist, supporting a Golf regulation by D₁ receptor usage. In contrast, the increases of Golf levels in patients were not affected by the duration of L-dopa treatment but correlated with duration of disease. In conclusion, our results revealed in the parkinsonian putamen a prolonged elevation of Golf levels that may lead to a persistent D₁ receptor hypersensitivity and contribute to the genesis of long-term complications of L-dopa.

Key words: Parkinson disease; dopamine; G-protein; striatum; L-dopa; 6-hydroxydopamine

---

Received Feb 25, 2004; revised June 13, 2004; accepted June 13, 2004.

This article has been cited by other articles:

				X. Zhang, P. E. Andren, P. Greengard, and P. Svenningsson Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of Parkinsonism PNAS, February 12, 2008; 105(6): 2163 - 2168. [Abstract] [Full Text] [PDF]

				D. B. Putterman, A. C. Munhall, L. B. Kozell, J. K. Belknap, and S. W. Johnson Evaluation of Levodopa Dose and Magnitude of Dopamine Depletion as Risk Factors for Levodopa-Induced Dyskinesia in a Rat Model of Parkinson's Disease J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 277 - 284. [Abstract] [Full Text] [PDF]

				E. Santini, E. Valjent, A. Usiello, M. Carta, A. Borgkvist, J.-A. Girault, D. Herve, P. Greengard, and G. Fisone Critical Involvement of cAMP/DARPP-32 and Extracellular Signal-Regulated Protein Kinase Signaling in L-DOPA-Induced Dyskinesia J. Neurosci., June 27, 2007; 27(26): 6995 - 7005. [Abstract] [Full Text] [PDF]

				N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help