Modulation of adenosine concentration by opioid receptor agonists in rat striatum.
There is evidence that adenosine and morphine interact in the striatum. However, little is known about the precise role of the opioid receptor subtypes implicated in the modulation of adenosine tissue concentration and in adenosine receptor expression and function. We sought to evaluate, in the absence of withdrawal symptoms, the effects of the short-term administration of selective mu-, delta- or kappa-opioid receptor agonists on adenosine concentration and on adenosine A(2A) receptor function in rat striatum. Adenosine A(2A) receptor was chosen because the neuronal sub-population expressing this receptor coexpresses enkephalin, suggesting that adenosine A(2A) receptor may be regulated by opioid receptor agonists. Oxymorphone hydrochloride mu-opioid receptor agonist, 6 mg/kg/day), +[-(5 alpha,7 alpha, 8 beta)-(-)-N-methyl-N(7-(1-pyrrolidinyl)1-oxaspiro (4.5)dec-8-yl) benzenacetamide] (U69593) (kappa-opioid receptor agonist, 0.75 mg/kg/day), and (+)-4[(alpha R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) (SNC80) (delta-opioid receptor agonist, 9 mm/kg/day), or vehicle, were administered i.p 3 x daily during 5 days to groups of rats (n=6). We also investigated the effects of opioid receptor agonists on adenosine uptake by striatal cell extracts. We found that administration of mu- or delta-opioid receptor agonists significantly decreased adenosine uptake in striatal cell extracts and increased adenosine concentration (mean+24% and +45% for mu- and delta-opioid receptor agonist, respectively, relative to controls). None of the receptor agonists tested induced obvious modifications of adenosine A(2A) receptor function. However, the delta-opioid receptor agonist induced an increase in adenosine A(2A) mRNA expression (mean 44%). We conclude that mu and delta receptor agonists inhibit adenosine uptake by striatal cell extracts and increase adenosine concentrations in rat striatum.
Halimi
G
G
UMR CNRS 6560, Laboratoire de Biochimie et d'Ingéniérie des Protéines, Faculté de Médecine Secteur Nord, Bd Pierre Dramard, 13916 Cedex, Marseille, France.
Devaux
C
C
Clot-Faybesse
O
O
Sampol
J
J
Legof
L
L
Rochat
H
H
Guieu
R
R
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D044482:Benzeneacetamides; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007274:Injections, Intraperitoneal; D010111:Oxymorphone / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000235:genetics
D001549:Benzamides; D044482:Benzeneacetamides; D010627:Phenethylamines; D010879:Piperazines; D058906:Purinergic P1 Receptor Agonists; D011759:Pyrrolidines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D010111:Oxymorphone; C045444:U 69593; D000241:Adenosine