Accumulation of adenosine 3',5'-monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists. II. Studies on mechanisms underlying the interaction with adenosine.

Incubation of slices of rat cerebral cortex with the calcium ionophore A23187 produced small increases in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP). While low concentrations of Ca2+ ions (e.g., 200 microM) were sometimes necessary, the presence of adenosine (e.g., 50 microM) was essential; no effect of ionophore was observed when isoproterenol or isobutylmethylxanthine was substituted for adenosine. These results are consistent with the previously advanced hypothesis that stimulation of alpha-adrenergic receptors in this issue may cause calcium mobilization and thereby produce a calmodulin-mediated stimulation of adenylate cyclase. However, there is no apparent explanation for the requirement for adenosine. In addition, the possibility that additional mechanisms may be operating was suggested by experiments in which the incorporation of 3H-adenine into cyclic AMP was examined under steady-state conditions. While brief exposure to 3H-adenine after maximal adenosine- or isoproterenol-induced accumulations had been achieved led to small increases in the specific activity of cyclic AMP, the combination of norepinephrine and adenosine (plus propranolol) produced substantial decreases in the specific activity of cyclic AMP. Since the rate of incorporation of radioactivity did not keep pace with the expansion of the cyclic AMP pool, it is possible that norepinephrine also caused some reduction in the rate of cyclic AMP degradation under these conditions. Other interpretations of these results are discussed.