Early changes in adenosine A(1) receptors in cerebral cortex slices submitted to in vitro ischemia

The effects of brain ischemia on the maximum binding capacity (B-max) and a ffinity (K-d) of A(1) receptors were studied in the rat cerebral cortex, wi th an in vitro approach. The results were correlated with changes in H-3-ad enosine release, studied under identical experimental conditions. Fifteen m inutes of in vitro 'ischemia' (hypoxic, glucose-free medium) induced a sign ificant increase in both B-max (2398 +/- 132 fmol/mg protein, 151% of the c ontrol, P < 0.05) and in K-d (2.43 +/- 0.12 nM, 161% of the control, P < 0. 01). At the same time, an increase in tritium efflux from [H-3]-adenosine l abeled cerebral cortex slices to 324% of the control was observed. A trend toward normalization was evident 5-15 min after 'reoxygenation' (restoring normal medium), but the binding parameters were still altered after 60 min (B-max 2110 +/- 82 fmol/mg protein, K-d 2.26 +/- 0.14 nM, P < 0.01 vs the c orresponding control) as was adenosine release (196% of the control). These findings suggest that the increased availability of adenosine and its rece ptors may be a defense mechanism against ischemic injury, while the reduced affinity of A(1) receptors, possibly due to desensitization, may be a sign of ischemia-induced cellular damage. (C) 1999 Elsevier Science Ltd. All ri ghts reserved.