Role of Presynaptic Purinoceptors and Cyclic AMP on the Noradrenaline Release in Cat Cerebral Arteries

— Field electrical stimulation (ES), K+ (50 mM) or ionophore X-537A (0.01 mM) induced tritium release from cat cerebral arteries preincubated with [3H]noradrenaline (NA). Adenosine and AMP (0.5 mM) did not modify tritium release caused by ionophore X-537A, but these agents and ATP (0.5 mM) significantly reduced that elicited by ES and K+; this reduction was antagonized by 1-methyl-3-isobutylxanthine (MIX; 0.05 mM). Inosine (0.5 mM) and the agonist of purinergic A2-receptors, 5′ N-ethylcarboxamide adenosine (NECA; 0.5 mM) had no effect, but the agonist of purinergic A1-receptors L-N6-phenylisopropyl adenosine (L-PIA; 0.1 mM) diminished tritium efflux caused by ES and K+. The adenosine inhibition of ES-induced radioactivity release was not affected by indomethacin (0.05 mM). MIX (0.05 mM) increased tritum release evoked by ES and K+. Agents that increase intracellular cyclic (c)AMP levels, such as dibutyryl cAMP (0.5 mM), the phosphodiesterase inhibitor Ro 20–1724 (01 mM), and the activators of adenylate cyclase, forskolin (0.005 mM) and NaF (2 mM) reduced tritium secretion elicited by ES and K+. However, the intracellular increase of cyclic GMP (cGMP) caused by 8-Br-cGMP did not affect this secretion. Dipyridamole (0.05 mM) and the adenosine deaminase inhibitor erythro-9-2-hydroxy-3 nonyl adenosine (EHNA; 0.1 mM) also produced inhibition of tritium secretion elicited by ES and K4. Dipyridamole reduced both the uptake of [3H]NA and [3H]adenosine. These results indicate that in these vessels: (1) presynaptic inhibition of exocytotic NA release induced by adenosine, ATP, and AMP is mainly mediated by purinoceptors of the A1-subtype, without participation of prostaglandins; (2) the nonexocytotic release is not presynaptically modulated; (3) intracellular increases of cAMP, but not of cGMP, reduced NA release; and (4) the effects of dipyridamole and EHNA appear to be mediated by augmentation of intracellular levels of adenosine by preventing its neuronal uptake and its adenosine deaminase inactivation, respectively.