A cautionary note: the actions of adenosine agonists and antagonists may be reversed under certain conditions in primary cultures.
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.
Brooke
S M
SM
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA. sheila.brooke@stanford.edu
Sapolsky
R M
RM
D015762:2-Chloroadenosine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D015762:2-Chloroadenosine; D013806:Theophylline; C028322:8-phenyltheophylline