The selective mGlu(5) receptor agonist CHPG inhibits quinpirole-induced turning in 6-hydroxydopamine-lesioned rats and modulates the binding characteristics of dopamine D(2) receptors in the rat striatum: interactions with adenosine A(2a) receptors.
In 6-hydroxydopamine-lesioned rats, the selective mGlu(5) receptor agonist (RS)-2-Cholro-5-Hydroxyphenylglycine (CHPG, 1-6 microg/10 microl intracerebroventricularly) significantly inhibited contralateral turning induced by quinpirole and, to a lesser extent, that induced by SKF 38393. The inhibitory effects of CHPG on quinpirole-induced turning were significantly potentiated by an adenosine A(2A) receptor agonist (CGS 21680, 0.2 mg/kg IP) and attenuated by an A(2A) receptor antagonist (SCH 58261, 1 mg/kg IP). In rat striatal membranes, CHPG (100-1,000 nM) significantly reduced the affinity of the high-affinity state of D(2) receptors for the agonist, an effect potentiated by CGS 21680 (30 nM). These results show the occurrence of functional interactions among mGlu(5), adenosine A(2A), and dopamine D(2) receptors in the regulation of striatal functioning, and suggest that mGlu(5) receptors may be regarded as alternative/integrative targets for the development of therapeutic strategies in the treatment of Parkinson's disease.
Popoli
P
P
Department of Pharmacology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. patrizia.popoli@iss.it
Pèzzola
A
A
Torvinen
M
M
Reggio
R
R
Pintor
A
A
Scarchilli
L
L
Fuxe
K
K
Ferré
S
S
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D007839:Functional Laterality; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine; D010648:Phenylacetates / Q000008:administration & dosage / Q000494:pharmacology*; D019257:Quinpirole / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013563:Sympathectomy, Chemical
C107349:2-chloro-5-hydroxyphenylglycine; D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D010648:Phenylacetates; D043705:Receptor, Adenosine A2A; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D005998:Glycine; D004298:Dopamine