Low efficacy adenosine A1 agonists inhibit striatal acetylcholine release in rats improving central selectivity of action
article
The objective of this study was to characterize the effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and its low efficacy derivatives 2′-deoxy-CPA (2DCPA), 3′-deoxy-CPA (3DCPA), 8-ethylamino-CPA (8ECPA) and 8-butylamino-CPA (8BCPA) on the release of acetylcholine (ACh) using intrastriatal microdialysis. These low efficacy agonists exhibited lower effects on the cardiovascular system than CPA. A concentration-dependent inhibition of ACh release was observed with a maximum of 60.5±2.4% for CPA, 42.5±2.3% for 2DCPA, 45.3±5.8% for 3DCPA, 57.1±1.4% for 8ECPA and 93.1±10.9% for 8BCPA, respectively. This effect was counteracted by the adenosine A1 receptor antagonist 8-cyclopentyltheophylline. These findings show that low efficacy adenosine A1 agonists inhibit striatal ACh release equally effective as CPA, suggesting that central nervous system-selective actions can be obtained with these compounds. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
Topics
AcetylcholineAdenosineAdenosine A1 receptorLow efficacy agonistMicrodialysisTissue selectivity2' deoxy 6 n cyclopentyladenosine3' deoxy 6 n cyclopentyladenosine6 n cyclopentyladenosine8 butylamino 6 n cyclopentyladenosine8 cyclopentyltheophylline8 ethylamino 6 n cyclopentyladenosineAcetylcholineAdenosine A1 receptor agonistUnclassified drugAcetylcholine releaseAnimal experimentAnimal tissueCardiovascular systemControlled studyCorpus striatumDose responseDrug effectDrug efficacyMaleMicrodialysisNonhumanRatAnimalsDose-Response Relationship, DrugMicrodialysisNeostriatumRats, WistarReceptor, Adenosine A2BReceptors, Purinergic P1Reproducibility of ResultsSensitivity and Specificity6 n cyclopentyladenosine, 41552-82-38 cyclopentyltheophylline, 35873-49-5Acetylcholine, 51-84-3, 60-31-1, 66-23-9Adenosine, 58-61-7;N(6)-cyclopentyladenosine, 41552-82-3Receptor, Adenosine A2BReceptors, Purinergic P1
TNO Identifier
237094
ISSN
0304-3940
Source
Neuroscience Letters, 343(1), pp. 57-61.
Pages
57-61
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