title: Newly synthesized noradrenaline mediates the alpha 2-adrenoceptor inhibition of [3H]5-hydroxytryptamine release induced by beta-phenylethylamine in rat hippocampal slices.
abstract: In slices of the rat hippocampus, alpha 2-adrenoceptors located presynaptically on serotonergic nerve terminals modulate the electrically evoked calcium-dependent release of [3H]serotonin [( 3H]5HT). We have investigated the effects of a naturally occurring trace amine, beta-phenylethylamine (beta-PEA), on noradrenergic transmission in the rat hippocampus. Under experimental conditions in which MAO of type B is inhibited by deprenyl-exposure to beta-PEA (0.1-10 microM) facilitates the spontaneous outflow of [3H]noradrenaline and inhibits the electrically evoked release of [3H]5HT. The inhibitory effect of beta-PEA (3 microM) on the evoked release of [3H]5HT was antagonized by the alpha 2-adrenoceptor antagonist idazoxan at 1 microM, and by pretreatment with alpha-methyl-p-tyrosine (alpha-MpT, 300 mg/kg i.p., 2 h). The inhibition of tyrosine hydroxylase activity by alpha-MpT does not modify the inhibition of the evoked release of [3H]5HT by the alpha 2-adrenoceptor agonist, 6-fluoronoradrenaline, or the serotonin receptor agonist, 5-methoxytryptamine. Pretreatment with the neurotoxin DSP4 (50 mg/kg i.p., 10 days) markedly antagonized the inhibitory action of beta-PEA on [3H]5HT release. These results indicate that the noradrenaline-releasing action of beta-PEA inhibits the electrically evoked release of [3H]5HT through the activation of alpha 2-adrenoceptors. This inhibitory effect appears to be mediated exclusively through the release of newly synthesized noradrenaline, and does not involve the direct activation by beta-PEA of the inhibitory 5HT autoreceptors which modulate [3H]5HT release in the rat hippocampus.
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003714:Denervation; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000096:biosynthesis / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D001596:Benzylamines; D004146:Dioxanes; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D014363:Tryptamines; C029261:phenethylamine; D012701:Serotonin; C015293:indopan; C012102:DSP 4; D009638:Norepinephrine; D019329:Idazoxan