Effects of the adenosine A1 receptor allosteric modulators PD 81,723 and LUF 5484 on the striatal acetylcholine release
article
The objective of the present study was to characterize the adenosine A1 receptor allosteric enhancing and antagonistic actions of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(3,4-dichlorophenyl) methanone (LUF 5484) and (2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluoromethyl)phenyl]methanone (PD 81,723) on striatal acetylcholine release. Upon local administration in conscious rats, LUF 5484 or PD 81,723 caused a concentration-dependent increase of extracellular acetylcholine levels of approximately 40%, which was similar to that obtained by the selective adenosine A1 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine (8CPT) and N6-cyclopentyl-9-methyladenine (N0840). In interaction experiments, LUF 5484 or PD 81,723 did not change the inhibition of acetylcholine release by the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA), whereas 8CPT caused an eightfold rightward shift. Acetylcholine concentrations were diminished with 62±3%, 48±11% and 56±9% by CPA, CPA+LUF 5484 and CPA+PD 81,723, respectively. In conclusion, the antagonistic action of LUF 5484 and PD 81,723 seems to counteract the putative allosteric actions with respect to the reduction of striatal acetylcholine release. © 2002 Elsevier Science B.V. All rights reserved. Chemicals/CAS: Acetylcholine, 51-84-3; PD 81723, 132861-87-1; Receptors, Purinergic P1; Thiophenes.
Topics
TNO Identifier
236776
ISSN
00142999
Source
European Journal of Pharmacology, 454(2-3), pp. 177-182.
Pages
177-182
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