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Adenosine A2A and group I metabotropic glutamate receptors synergistically modulate the binding characteristics of dopamine D2 receptors in the rat striatum
- Source :
- Neuropharmacology. 38:129-140
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- There is experimental evidence for the existence of interactions between metabotropic glutamate (mGlu), adenosine and dopamine receptors in the striatum. In membrane preparations from rat striatum the group I and II mGlu receptor agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S-3R-ACPD) was found to modulate the binding characteristics of D2 receptors in a similar manner as the A2A receptor agonist 2-[p-(2-carboxyethyl)phenthylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680), with a significant decrease in the affinity of the high-affinity state of D2 receptors for dopamine. The effect of 1S-3R-ACPD was mimicked by (+/-)-trans-ACPD (t-ACPD; a racemic mixture of 1S-3R-ACPD and its inactive isomer 1R-3S-ACPD) and by the selective group I mGlu receptor agonist 3,5-dihydroxyphenylglycine (DHPG) and it was counteracted by the selective group I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxilic acid (AIDA), but not by the the group II and III mGlu receptor antagonist (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG) or the adenosine receptor antagonist 8-phenyltheophylline. Furthermore, a strong synergistic effect was observed when the striatal membranes were exposed to both CGS 21680 and 1S-3R-ACPD. In agreement with the biochemical results, in unilaterally 6-OH-dopamine lesioned rats 1S-3R-ACPD counteracted the turning behaviour induced by the D2 receptor agonist quinpirole, but not by the D1 receptor agonist SKF 38393, and it synergistically potentiated the antagonistic effect of CGS 21680 on quinpirole-induced turning behaviour.
- Subjects :
- Male
Agonist
medicine.medical_specialty
Quinpirole
Receptor, Adenosine A2A
Rotation
medicine.drug_class
receptor
Parkinson's disease
Motor Activity
Biology
Receptors, Metabotropic Glutamate
Adenosine receptor antagonist
Striatum
Rats, Sprague-Dawley
Radioligand Assay
Cellular and Molecular Neuroscience
Internal medicine
Dopamine receptor D2
Salicylamides
medicine
Animals
Pharmacology
Receptors, Dopamine D2
Receptors, Purinergic P1
Benzazepines
Receptor antagonist
Corpus Striatum
Rats
Metabotropic receptor
Endocrinology
Raclopride
Competitive antagonist
Metabotropic glutamate receptor
Metabotropic glutamate (mGlu) receptor
Dopamine Agonists
Adenosine A(2A) receptor
Dopamine Antagonists
Dopamine D
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Receptor-receptor interaction
Endogenous agonist
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....e53d01563faa2f69004f9d3654ea0b68