Vol. 291, Issue 1, 7-11, October 1999

Modulation of Norepinephrine Release from Sympathetic Neurons of the Rabbit Aorta by Prejunctional Prostanoid Receptors¹

Tenna Juul Jensen and Ove A. Nedergaard

Department of Pharmacology, School of Medicine, Odense University, Odense, Denmark

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 ₂-adrenoceptors. Electrical field stimulation was used to evoke ³H overflow. Prostaglandin (PG)E₂ (10⁹ to 3 × 10⁷ M) reduced the stimulation-evoked ³H overflow; the pEC₅₀ value was 8.3, and E_max value was 98%. This effect was also seen with PGE₁, PGD₂, PGF₂, 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) > PGF₂ (6.0) > PGD₂ (<5.0). This rank order suggests that these agents act on prejunctional prostaglandin receptors of the EP₃ subtype. The stable thromboxane A₂ analog U46619 (9,11-dideoxy-11, 9-epoxymethano-PGF₂) 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 × 10⁵ M. 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.