Abstract:
:Adenosine and its agonists exert a depressant effect on neuronal activity by interacting with the adenosine A1 receptor. There is now also evidence for electrophysiological effects mediated by adenosine receptors other than the A1 type, possibly A2 receptors. A1 and A2 receptor-induced changes in the electrical properties of neuronal membranes were investigated by intracellularly recording from rat hippocampal CA1 neurons and using the adenosine agonists, 5'-N-ethylcarboxamidoadenosine (NECA) and R-phenylisopropyladenosine (PIA), and the unselective A1 and A2 receptor antagonist, theophylline and the selective A1 receptor antagonist, 8-cyclopenthyl-1,3-dipropylxanthine (DPCPX). PIA and NECA produced an inhibitory effect which was blocked by DPCPX and thus was mediated by A1 receptors. PIA produced inhibition at lower concentrations (0.1-1 mumol/l) than NECA (0.5-10 mumol/l), whereas at high concentrations (2.5 mumol/l) it exerted a dual effect, i.e. either an inhibitory or an excitatory one. During simultaneous perfusion with the A1 receptor antagonist DPCPX, PIA produced concentration-dependent excitatory effects at concentrations above 1 mumol/l. These excitatory effects were blocked by theophylline. DPCPX produced excitation that was enhanced by NECA. Forskolin caused no change in the membrane properties. It is concluded that (1) NECA and PIA affect the membrane properties not only by an action on the A1 but also on non-A1 receptors, because the excitatory effects of PIA and NECA were insensitive to DPCPX and abolished by theophylline; (2) PIA and NECA are more potent at A1 than at A2 receptors; (3) PIA is more potent than NECA at A1 and A2 receptors; (4) effects mediated by A2 receptors prevail over those mediated by A1 receptors when A2 receptors are activated; and (5) the non-A1 receptor-mediated effects are independent of an increased formation of cAMP.
journal_name
Brain Resjournal_title
Brain researchauthors
Ameri A,Jurna Idoi
10.1016/0006-8993(91)91160-3subject
Has Abstractpub_date
1991-04-12 00:00:00pages
69-78issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(91)91160-3journal_volume
546pub_type
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