TONIC ADENOSINE A(2A) RECEPTOR ACTIVATION MODULATES NICOTINIC AUTORECEPTOR FUNCTION AT THE RAT NEUROMUSCULAR-JUNCTION

• Type: Article in International Scientific Journal
• Date: 1994

Authors

Paulo Correia de Sá (Author) Other; RIBEIRO, JA (Author) Other

Journal

Title: European Journal of Pharmacology

Vol. 271

Pages: 349-355

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 59 Citations

Scopus - 62 Citations

Other information

Authenticus ID: P-001-J6B

DOI: 10.1016/0014-2999(94)90793-5

Abstract (EN): The influence of the activation of presynaptic adenosine receptors on nicotinic autofacilitation of electrically evoked [H-3]acetylcholine release from rat phrenic motor nerve terminals was investigated. Blocking the adenosine A(2A) receptor with 3,7-dimethyl-1-propargylxanthine (DMPX, 10 mu M) greatly potentiated, whereas the adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 2.5 nM), partially prevented the facilitatory effect of the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 1 mu M, 3 min), on evoked [H-3]acetylcholine release. The adenosine A(2A) receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadenosine (CGS 21680C, 3 nM), but not the adenosine A(1) receptor agonist, R-N-6-phenylisopropyl adenosine (R-PIA, 300 nM), partially blocked the DMPP (1 mu M) facilitation. Forskolin (3 mu M) mimicked the attenuation caused by CGS 21680C; inhibition of adenylate cyclase with N-(as-2-phenylcyclopentyl)azacyclo-tridecan-2-imine hydrochloride (MDL 12,330A, 10 mu M) markedly enhanced the facilitatory effect of DMPP (1 mu M). Prolonged exposure to a high concentration of DMPP (10 mu M, 15 min) decreased evoked tritium outflow. The decrease in evoked [3H]acetylcholine release following prolonged exposure to DMPP was augmented by pretreatment with CGS 21680C (3 nM) and forskolin (3 mu M), and was abolished by inactivating endogenous adenosine with adenosine deaminase (0.5 U/ml). It is concluded that tonic adenosine A(2A) receptor activation regulates nicotinic acetylcholine autofacilitation. This action is likely to be mediated through an adenylate cyclase/cyclic AMP-dependent mechanism.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7