Effects of protein kinase C activation on the sensitivity of pre- and postsynaptic adenosine receptors

Prolonged incubation of hippocampal brain slices at reduced temperature immediately after preparation ("cold shock" treatment) has been shown to lead to an extremely persistent activation of protein kinase C (PKC). Because of the numerous suggestions that adenosine receptor sensitivity can be modulated by PKC, we have characterized the changes in both pre- and postsynaptic adenosine A(1) receptor sensitivity following such treatment. The maximal effect of activation of postsynaptic A(1) receptors was significantly reduced, although there was no change in the EC50 value. On the other hand, the sensitivity of presynaptic adenosine receptors was slightly although significantly increased (the EC50 value was reduced), with no apparent change in the maximal effect. Finally, the effect of dipyridamole was reduced in these slices, suggesting that its ability to inhibit adenosine transport was reduced. These results suggest that the cold shock treatment does not affect PKC activity in all cellular compartments and that, in particular, PKC-dependent changes in nerve terminal and somatic A(1) receptors are markedly different. Drug Dev. Res. 45:329-335, 1998. Published 1998 Wiley-Liss, Inc.dagger.