ADENOSINE MODULATION OF HISTAMINE-STIMULATED PHOSPHOINOSITIDES METABOLISM IN RAT CORTICAL SLICES

Adenosine structural analogues exert a significant and dose-dependent inhibition on inositol phospholipid hydrolysis elicited in rat cortical slices by mM histamine concentrations. The rank order of potency of the utilized agonists and the complete antagonism by a selective A1-receptor blocker suggest that this effect is mediated by the activation of the adenosine A1 receptor subtype. Adenosine modulation is selective for histamine, since no effect is exerted by adenosine analogues on either basal or carbachol-, glutamate-, quisqualate- and noradrenaline-stimulated inositol phosphate generation. A detailed analysis of adenosine effects on histamine-dependent phosphoinositides metabolism reveals that the effect of adenosine analogues is byphasic, consisting in an enhancement of histamine activity at low histamine concentrations, which is turned into an inhibition when phosphoinositides hydrolysis is maximally stimulated by histamine. It is concluded that adenosine selectively modulates histamine-stimulated inositol-phosphates production in rat cortex via activation of A1 receptors, and that such an effect is dependent upon the degree of activation of the target system.