TY - JOUR T1 - Modulation of Norepinephrine Release from Sympathetic Neurons of the Rabbit Aorta by Prejunctional Prostanoid Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 7 LP - 11 VL - 291 IS - 1 AU - Tenna Juul Jensen AU - Ove A. Nedergaard Y1 - 1999/10/01 UR - http://jpet.aspetjournals.org/content/291/1/7.abstract N2 - 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, andEmax value was 98%. This effect was also seen with PGE1, PGD2, PGF2α, 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) > PGF2α(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-PGF2α) 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. The American Society for Pharmacology and Experimental Therapeutics ER -