Adenosine--norepinephrine interactions on cyclic AMP generating system in human tumoral brain slices

Many experimental findings suggest that the administration of exogenous Norepinephrine (NE), in cerebral cortical slices surviving in vitro, increases cyclic AMP (cAMP) levels, although the NE receptor turns out to be different for the different animal species. Likewise, in the same experimental model, Adenosine (A) increases the cAMP intracellular levels. Furthermore, A sites seem to be linked with adrenoreceptors related to the cAMP-generating system. In this report we studied the interaction of NE on the cAMP system of human cerebral tissue slices, normal and tumoral. In the normal slices, NE increases cAMP levels in a dose-dependent manner, probably through beta-receptors; in fact, Propranolol counteracts this effect. Also A induces a dose-dependent rise of cAMP levels; Theophylline prevents, while low doses of Dipyridamole potentiate, this effect. The contemporaneous administration of NE and A produces an effect on cAMP levels greater than that displayed by each drug alone. Probably the enhanced cAMP increase is due to the endogenous release, evoked by NE. In fact, Propranolol reduces, but does not completely prevent, the effect of NE. In cortical tumor slices, the effect of NE on the cAMP-generating system is very reduced. This suggests that the membrane damage of neoplastic cells affects the availability of adrenoreceptors. On the other hand, the responsiveness of A sites is deeply altered. The receptor antagonists or the re-uptake inhibitors of this Adenine nucleotided do not exert their effect selectively.