Abstract

The pharmacological properties and subtypes of prostanoid receptors involved in the prejunctional modulation of [³H]norepinephrine release from sympathetic neurons were studied using isolated rabbit aorta. Rings preincubated with [³H]norepinephrine were washed with physiological salt solution that contained cocaine plus corticosterone, uptake₁ and uptake₂ inhibitors, respectively, and rauwolscine to block prejunctional α₂-adrenoceptors. Electrical field stimulation was used to evoke ³H overflow. Prostaglandin (PG)E₂ (10⁻⁹ to 3 × 10⁻⁷m) reduced the stimulation-evoked³H overflow; the pEC₅₀ value was 8.3, andE_max value was 98%. This effect was also seen with PGE₁, PGD₂, PGF_2α, the EP₁/EP₃ receptor agonist sulprostone, the EP₂/EP₃ receptor agonist misoprostol, and the EP₁/IP receptor agonist iloprost; the rank order (pEC₅₀) was sulprostone (8.4) > PGE₂ (8.3) > misoprostol (8.1) > PGE₁ (7.9) > PGF_2α(6.0) > PGD₂ (<5.0). This rank order suggests that these agents act on prejunctional prostaglandin receptors of the EP₃ subtype. The stable thromboxane A₂analog U46619 (9,11-dideoxy-11α, 9α-epoxymethano-PGF_2α) slightly reduced the stimulation-evoked ³H overflow. The FP receptor agonist fluprostenol and the EP₂ receptor agonist butaprost had no effect. The EP receptor antagonist AH6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) did not alter the inhibitory effect of PGE₂ and sulprostone. AH6809 did not modulate the stimulation-evoked ³H overflow. This suggests that prejunctional EP₁ receptors are not involved. The IP receptor agonist cicaprost reduced the ³H overflow only at concentrations higher than 3 × 10⁻⁵m. We conclude that the postganglionic sympathetic neurons in rabbit aorta are endowed with prejunctional inhibitory EP₃ receptors. FP and IP receptors are not present, and the possible presence of inhibitory DP receptors requires further study.