1. Adenosine A2A and group I metabotropic glutamate receptors synergistically modulate the binding characteristics of dopamine D2 receptors in the rat striatum
- Author
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Kjell Fuxe, Rosaria Reggio, Patrizia Popoli, J. Kehr, Sergi Ferré, Roberto Rimondini, Ferre S., Popoli P., Rimondini R., Reggio R., Kehr J., and Fuxe K.
- 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 - 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.
- Published
- 1999