Prostaglandins of the E series inhibit monoamine release via EP3 receptors: proof with the competitive EP3 receptor antagonist L-826,266 |
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Authors: | J. Günther K. Schulte D. Wenzel B. Malinowska E. Schlicker |
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Affiliation: | 1. Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universit?t Bonn, BMZ, Sigmund-Freud-Str. 25, 53127, Bonn, Germany 2. Institut für Physiologie I, Rheinische Friedrich-Wilhelms-Universit?t Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany 3. Zak?ad Fizjologii Do?wiadczalnej, Uniwersytet Medyczny, ul. Mickiewicza 2A, 15-089, Bia?ystok, Poland
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Abstract: | Prostaglandin E2 (PGE2) and its analogue sulprostone inhibit noradrenaline and serotonin release in rodent tissues. We examined whether the receptor involved is blocked by the EP3 antagonist L-826,266, whether such receptors also occur on central cholinergic neurones and retinal dopaminergic cells, whether PGE2 is produced by the degradation of the endocannabinoid virodhamine and whether EP3 receptor activation stimulates 35S-GTPγS binding. Transmitter release was studied as electrically evoked tritium overflow in superfused tissues preincubated with 3H-noradrenaline (which in the guinea pig retina labels dopaminergic cells), 3H-serotonin or 3H-choline. 35S-GTPγS binding, a measure of G protein activation, was studied in mouse and guinea pig hippocampal membranes. L-826,266 antagonised the effect of sulprostone on noradrenaline release in the rat cortex, yielding a Schild plot-based pA2 value of 7.56. Apparent pA2 values in mouse cortex and rat vas deferens (noradrenaline release) and rat cortex (serotonin release) were 7.55, 7.87 and 7.67, respectively. PGE2 did not affect acetylcholine release in rat brain and dopamine release in guinea pig retina. In seven mice tissues, noradrenaline release was inhibited by sulprostone but not affected by virodhamine. 35S-GTPγS binding was not altered by sulprostone but stimulated by the cannabinoid agonist WIN 55,212-2. Prostaglandins of the E series inhibit monoamine release via EP3 receptors at which L-826,266 is a competitive antagonist. EP3 receptors that inhibit transmitter release are not present on central cholinergic neurones and retinal dopaminergic cells. Virodhamine is not converted to PGE2. An EP3 receptor model based on 35S-GTPγS binding could not be identified. |
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