Prostanoid receptors of the EP3 subtype mediate the inhibitory effect of prostaglandin E2 on noradrenaline release in the mouse brain cortex

Abstract

Mouse or rat brain cortex slices were preincubated with 3H-noradrenaline and superfused with physiological salt solution containing desipramine. We studied the effects of prostaglandin E2 (PGE2), prostaglandin D2 (PGD2) and related drugs on the electrically evoked (50 mA, 2 ms, 0.3 Hz) tritium overflow. PGE2 inhibited the electrically evoked tritium overflow from mouse brain cortex slices; the maximum effect of PGE2 (79%) was attenuated by the alpha 2-adrenoceptor agonist talipexole (to 52%) and enhanced by the alpha 2-adrenoceptor antagonist rauwolscine (to 92%). Rauwolscine was added to the superfusion medium in all subsequent experiments. The effect of PGE2 was readily reversible upon withdrawal from the medium and remained constant upon prolonged exposure of the tissue to the prostanoid. Studies with EP receptor agonists, mimicking the inhibitory effect of PGE2, showed the following potencies (pIC50); sulprostone (8.22); misoprostol (8.00); PGE2 (7.74); PGE1 (7.61); iloprost (5.86). The concentration-response curve of PGE2 was marginally shifted to the right by the EP1 receptor antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2- carboxylic acid; apparent pA2 3.97) and by the TP receptor antagonist vapiprost (4.50). AH 6809, by itself, did not affect the evoked overflow whereas vapiprost increased it. PGD2 inhibited the evoked overflow at high concentrations (pIC50 4.90); this effect was not altered by the DP receptor antagonist BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2- hydroxyethylamino)hydantoin), which, by itself, did not affect the evoked overflow. Indometacin slightly increased the evoked overflow and tended to increase the inhibitory effect of PGE2. PGE2 inhibited the electrically evoked tritium overflow also in rat brain cortex slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Developing Pharmacotherapies for Cannabis and Cocaine Use Disorders

“…Convergent evidence supports this hypothesis. In an in vitro study of the effects of prostaglandin E 2 on electrically-evoked tritiated norepinephrine overflow, Exner and Schlicker found that prostaglandin E 2 inhibited the electrically-evoked norepinephrine tritium overflow from mouse and rat brain cortex slices [59]. Data from an earlier similarly designed study were consistent with those obtained by Exner and Schlicker [111].…”

Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

“…Previous studies have shown that EP 3 receptors on presynaptic nerve terminals regulate the release of neurotransmitters (Exner and Schlicker, 1995;Nakamura et al, 1998;Schlicker and Marr, 1997). Whether EP 3 receptors are present on glutamatergic terminals of presynaptic sites of the dl-PAG has not, to our knowledge, been reported although EP 3 immunoreactivity has been identified in the dl-PAG (Ek et al, 2000;Nakamura et al, 2000).…”

Immunohistochemical localization of prostaglandin EP3 receptor in the rat nervous system

“…Many pharmacologic studies have indicated that EP3R functions as a presynaptic receptor (Mantelli et al, 1991;Molderings et al, 1992Molderings et al, , 1994Exner and Schlicker, 1995;Reinheimer et al, 1998;Spicuzza et al, 1998). From the above-mentioned results of the dorsal rhizotomy experiments, it is inferred that the EP3R protein in the spinal dorsal horn is supplied through axons from dorsal root ganglion cells and is located on the presynaptic membrane.…”