title: Dopamine heteroreceptor complexes as therapeutic targets in Parkinson's disease.
abstract: BACKGROUND
  Several types of D2R and D1R heteroreceptor complexes were discovered in the indirect and direct pathways of the striatum, respectively. The hypothesis is given that changes in the function of the dopamine heteroreceptor complexes may help us understand the molecular mechanisms underlying the motor complications of long-term therapy in Parkinson's disease (PD) with l-DOPA and dopamine receptor agonists.
  
  
  METHODS
  In the indirect pathway, the potential role of the A2AR-D2R, A2AR-D2R-mGluR5 and D2R-NMDAR heteroreceptor complexes in PD are covered and in the direct pathway, the D1R-D3R, A1R-D1R, D1R-NMDAR and putative A1R-D1R-D3R heteroreceptor complexes.
  
  
  CONCLUSIONS
  One explanation for the more powerful ability of l-DOPA treatment versus treatment with the partial dopamine receptor agonist/antagonist activity to induce dyskinesias, may be that dopamine formed from l-DOPA acts as a full agonist. The field of D1R and D2R heteroreceptor complexes in the CNS opens up a new understanding of the wearing off of the antiparkinson actions of l-DOPA and dopamine receptor agonists and the production of l-DOPA-induced dyskinesias. It can involve a reorganization of the D1R and D2R heteroreceptor complexes and a disbalance of the D1R and D2R homomers versus non-dopamine receptor homomers in the direct and indirect pathways.
authors.affiliation: Karolinska Institutet, Department of Neuroscience , Retzius väg 8, 17177 Stockholm , Sweden +46 852 487 077 ; +46 8 315 721 ; Kjell.Fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000009:adverse effects / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D054333:Drug Partial Agonism; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D007980:Levodopa; D004298:Dopamine
keywords: G-protein-coupled receptors; Parkinson’s disease; allosteric receptor–receptor interactions; dimerization; dopamine D1 receptor; dopamine D2 receptor; dopamine heteroreceptor complexes; dopamine receptor agonists; dyskinesias; homodimerization; l-DOPA; motor complications; neurodegeneration