title: Desensitisation of the adenosine A1 receptor by the A2A receptor in the rat striatum.
abstract: The influence of the adenosine A2A receptor on the A1 receptor was examined in rat striatal nerve terminals, a model for other cells in which these receptors are coexpressed. Incubation of striatal synaptosomes with the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) caused the appearance of a low-affinity binding site for the A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA). This effect was blocked by the A2A receptor antagonist ZM241385 and by the protein kinase C inhibitor chelerythrine, but not by the protein kinase A inhibitor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004). The effect was not seen with striatal membranes or with hypotonically lysed synaptosomes. These results demonstrate a protein kinase C-mediated heterologous desensitisation of the A1 receptor by the A2A receptor.
authors.affiliation: Department of Pharmacology, University of Cambridge, England, U.K.
authors.forename: A K
authors.initials: AK
authors.lastname: Dixon
authors.forename: L
authors.initials: L
authors.lastname: Widdowson
authors.forename: P J
authors.initials: PJ
authors.lastname: Richardson
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013449:Sulfonamides; D013574:Synaptosomes / Q000737:chemistry / Q000201:enzymology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014316:Tritium; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D013449:Sulfonamides; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C058394:2-chloro-N(6)cyclopentyladenosine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011493:Protein Kinase C; D000241:Adenosine