Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·
 

Low efficacy adenosine A1 agonists inhibit striatal acetylcholine release in rats improving central selectivity of action

Publication files not online:

Author: Bueters, T.J.H. · Helden, H.P.M. van · IJzerman, A.P. · Danhof, M.
Type:article
Date:2003
Source:Neuroscience Letters, 1, 343, 57-61
Identifier: 237094
doi: doi:10.1016/S0304-3940(03)00311-2
Keywords: Acetylcholine · Adenosine · Adenosine A1 receptor · Low efficacy agonist · Microdialysis · Tissue selectivity · 2' deoxy 6 n cyclopentyladenosine · 3' deoxy 6 n cyclopentyladenosine · 6 n cyclopentyladenosine · 8 butylamino 6 n cyclopentyladenosine · 8 cyclopentyltheophylline · 8 ethylamino 6 n cyclopentyladenosine · Acetylcholine · Adenosine A1 receptor agonist · Unclassified drug · Acetylcholine release · Animal experiment · Animal tissue · Cardiovascular system · Controlled study · Corpus striatum · Dose response · Drug effect · Drug efficacy · Male · Microdialysis · Nonhuman · Rat · Animals · Dose-Response Relationship, Drug · Microdialysis · Neostriatum · Rats, Wistar · Receptor, Adenosine A2B · Receptors, Purinergic P1 · Reproducibility of Results · Sensitivity and Specificity · 6 n cyclopentyladenosine, 41552-82-3 · 8 cyclopentyltheophylline, 35873-49-5 · Acetylcholine, 51-84-3, 60-31-1, 66-23-9 · Adenosine, 58-61-7; · N(6)-cyclopentyladenosine, 41552-82-3 · Receptor, Adenosine A2B · Receptors, Purinergic P1

Abstract

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.