METABOLISM OF SEROTONIN IN THE VERTEBRATE BRAIN
Presynaptic Control of Serotonin Release. Slices were incubated in the presence of ('3)H-serotonin (('3)H-5-HT) and then superfused in lucite chambers with a Krebs-Ringer phosphate (KRP) solution. Tritium release was induced by electrical stimulation. Mouse cerebellum. Exogenous unlabeled serotonin (5-HT) decreased the basal and stimulated tritium overflow in a concentration-related manner, in the presence of the 5-HT uptake blocker fluoxetine. The inhibitory effect of 5-HT on stimulated tritium overflow was blocked by the simultaneous administration of methiothepin but not methysergide, both being 5-HT antagonists. Superfusion of the slices with a KRP Ca('2+)-free solution and also in the presence of EGTA reduced the basal and stimulated tritium overflow. Under the present experimental conditions 82% of the tritium recovered during stimulation appeared to be unmetabolized ('3)H-5-HT. Prostaglandins E(,2) and F(,2(alpha)) did not alter the basal and stimulated tritium overflow. However norepinephrine (NE) and dibutyryl cyclic guanosine monophosphate (dbcGMP) reduced both basal and stimulated tritium overflow. Phenoxybenzamine, an (alpha) antagonist, partially blocked the inhibitory effect of NE on stimulated tritium overflow. It is concluded that changes in stimulated tritium overflow reflect changes in ('3)H-5-HT release, that extracellular 5-HT is able to inhibit action potential-induced release of intraneuronal 5-HT. This inhibition is mediated through specific receptors of probable presynaptic location. Prostaglandins E(,2) and F(,2(alpha)) do not seem to play a role in the regulation of release of 5-HT. However the marked inhibitory effect of NE on 5-HT release appears to work by means of an (alpha) receptor, probably located on the presynaptic serotoninergic terminal. The inhibitory effect of dbcGMP on tritium overflow suggests that cGMP may mediate the presynaptic inhibitory mechanisms leading to a reduction of 5-HT release. Goldfish brain. Exogenous 5-HT did not alter the stimulated tritium overflow, but this was reduced when the superfusion was performed in Ca('2+)-free and in Ca('2+)-free-EGTA conditions. Eighty % of the tritium recovered during stimulation seemed to correspond to unmetabolized 5-HT. These findings suggest that the release of 5-HT from goldfish neurones is a process similar to that seen in mammals, e.g., a Ca('2+)-dependent mechanism, presumably involving exocytosis. However, it differs from the mammalian system since there do not appear to be presynaptic autoreceptors in the terminals of brain serotoninergic neurones. Monoamine Oxidase (MAO) in the Goldfish Brain. Tissue homogenates were incubated in vitro and MAO activity determined fluorometrically. Harmaline, clorgyline, deprenyl and pargyline inhibited MAO activity in a concentration-related manner with single sigmoid inhibition curves. MAO was more sensitive to inhibition by type A inhibitors (harmaline and clorgyline) than by a type B inhibitor (deprenyl). In conclusion, these results show that goldfish MAO appears to exist as a single form, with inhibitor sensitivities indicating that it is very similar to mammalian MAO type A.
HECTOR RAUL FIGUEROA,
"METABOLISM OF SEROTONIN IN THE VERTEBRATE BRAIN"
(January 1, 1981).
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