Early changes in adenosine A1 receptors in cerebral cortex slices submitted to in vitro ischemia |
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Authors: | Anna Siniscalchi Donata Rodi Stefania Gessi Franca Campi Pier A Borea |
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Institution: | Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara, 17, 44100 Ferrara, Italy |
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Abstract: | The effects of brain ischemia on the maximum binding capacity (Bmax) and affinity (Kd) of A1 receptors were studied in the rat cerebral cortex, with an in vitro approach. The results were correlated with changes in 3H-adenosine release, studied under identical experimental conditions. Fifteen minutes of in vitro ‘ischemia’ (hypoxic, glucose-free medium) induced a significant increase in both Bmax (2398±132 fmol/mg protein, 151% of the control, P<0.05) and in Kd (2.43±0.12 nM, 161% of the control, P<0.01). At the same time, an increase in tritium efflux from 3H]-adenosine labeled 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 (Bmax 2110±82 fmol/mg protein, Kd 2.26±0.14 nM, P<0.01 vs the corresponding control) as was adenosine release (196% of the control). These findings suggest that the increased availability of adenosine and its receptors may be a defense mechanism against ischemic injury, while the reduced affinity of A1 receptors, possibly due to desensitization, may be a sign of ischemia-induced cellular damage. |
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Keywords: | brain ischemia adenosine a1 receptor |
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