Modulation of noradrenaline release from the sympathetic nerves of human right atrial appendages by presynaptic EP3- and DP-receptors

Strips of human right atrial appendages were preincubated with [H-3]noradrenaline and then superfused with physiological salt solution containing inhibitors of uptake, and uptake(2). Tritium overflow was evoked by transmural electrical stimulation (standard frequency: 2 Hz). Prostaglandin E-2 (PGE(2)) inhibited the electrically evoked tritium overflow; at the highest concentration investigated, tritium overflow was reduced by about 80% and the pIC(50%) value was 7.14. The effect of PGE(2) was not affected by rauwolscine, which, by itself, increased the evoked overflow. Naproxen failed to affect the evoked tritium overflow and its inhibition by PGE(2). The inhibitory effect of PGE(2) on the electrically evoked tritium overflow was mimicked by prostaglandin E-1, the EP1/EP3-receptor agonist sulprostone and the EP2/EP3-receptor agonist misoprostol with the rank order of potency (pEC(50%)): sulprostone (7.68) > misoprostol (7.10) > PGE(1) (6.39). In contrast, PGF(2 alpha), the IP/EP1-receptor agonist iloprost and the stable thromboxane A(2) analogue U46619 (9,11-dideoxy-11 alpha,9 alpha-epoxy-methanoprostaglandin F-2 alpha) did not change evoked tritium overflow PGD(2) caused facilitation. These results suggest that the sympathetic nerve fibres innervating human atrial appendages are endowed with presynaptic inhibitory EP3 and facilitatory DP-receptors. The EP3-receptors appear not to be tonically activated and do not interact with the alpha(2)-autoreceptors.