Deletion of the adenosine A1 receptor gene does not alter neuronal damage following ischaemia in vivo or in vitro.
Extracellular adenosine is dramatically increased during cerebral ischaemia and is considered to be neuroprotective due to its inhibitory effect on synaptic transmission mediated by the adenosine A1 receptor (A1R). We investigated the importance of the A1R in a mouse model of global ischaemia and in a murine hippocampal slice culture model of in vitro ischaemia, using mice with the A1R gene deleted. In brains from mice lacking the A1R, damage induced by global ischaemia was similar to that in wild-type animals. In contrast, treatment with a selective A1R antagonist [8-cyclo-pentyl theophylline (8-CPT)], administered before the ischaemic insult in naive wild-type mice, exacerbated the neuronal damage following global ischaemia. Although the inhibitory action of adenosine on excitatory neurotransmission in hippocampal slices was lost in A1R knockout mice, there was no difference in damage between slices from wild-type and knockout mice after in vitro ischaemia. The results suggest that some effects of the A1R are compensated for in knockout animals.
Olsson
Tomas
T
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, SE-221 84, Sweden. tomas.olsson@expbr.lu.se
Cronberg
Tobias
T
Rytter
Anna
A
Asztély
Fredrik
F
Fredholm
Bertil B
BB
Smith
Maj-Lis
ML
Wieloch
Tadeusz
T
D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D043682:Receptor, Adenosine A1 / Q000172:deficiency* / Q000235:genetics*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline