A cautionary note: the actions of adenosine agonists and antagonists may be reversed under certain conditions in primary cultures.

Abstract:

:It is now generally accepted that adenosine has a neuroprotective role in the central nervous system. Agonists of adenosine such as 2-chloroadenosine (2-ClA) have been shown to be neuroprotective, while antagonists such as 8-phenyltheophylline (8-PT) increase neurotoxicity. However, paradoxical results have been reported with adenosine analogues, especially with respect to length of time of administration. We observe similarly contradictory findings with respect to 2-ClA and 8-PT actions in primary hippocampal cultures exposed to glutamate or kainic acid. We found 8-PT and 2-ClA had antagonist and agonist actions, respectively, only with acute (1 h) treatment; with chronic treatment (24 h), 2-ClA had no effects, while 8-PT had significant agonist actions. We also show that with variations in the type of culturing system, concentration, and pH that 8-PT's neurotoxic antagonist actions could be dramatically changed. We, therefore, present this paper as a cautionary note in experimenting with adenosine analogues.

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Brooke SM,Sapolsky RM

doi

10.1016/s0361-9230(99)00238-5

keywords:

subject

Has Abstract

pub_date

2000-03-01 00:00:00

pages

307-12

issue

4

eissn

0361-9230

issn

1873-2747

pii

S0361-9230(99)00238-5

journal_volume

51

pub_type

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