SUBCELLULAR DISTRIBUTION OF 5‐HYDROXYTRYPTAMINE IN RAT BRAIN DURING DEVELOPMENT: EFFECT OF DRUGS AND FASTING

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Abstract
Abstract— Distribution of brain 5‐HT content between the high‐speed supernatant and particulate fractions under normal and experimental conditions was studied in postnatal and adult rats. In adult and 35‐day‐old rats the 5‐HT content of the supernatant fraction was about 25% of that of the total homogenate and significantly higher than that in 1, 7 and 21‐day‐old rats. In 1‐day‐old rats fasting caused an increase of 100% in the turnover, 50% in the content and no alteration in the subcellular distribution of brain 5‐HT, which suggests that under normal conditions 5‐HT stores may be filled near to capacity. After 5‐hydroxytryptophan administration, the 5‐HT content of the adult rat brain increased 3‐fold and that of the supernatant fraction to 35% of 5‐HT content of the total homogenate. In postnatal rats, the brain 5‐HT content rose to an adult level and the supernatant 5‐HT percentage to a markedly higher than adult level, probably because of the known higher than adult 5‐hydroxytryptophan decarboxylase activity of brain capillaries. Administration of tranylcypromine to adult rats caused a 2.6‐fold increase of brain 5‐HT content and a slight increase of the supernatant 5‐HT percentage. At various times after the administration of the MAO inhibitors (tranylcypromine or pargyline) and fasting to the 1‐day‐old rats, brain 5‐HT content increased 4, 5 and 7‐fold, respectively, and the supernatant 5‐HT rose consistently and, as in the adult, to about 30% of the 5‐HT content of the total homogenate. After pargyline following reserpine pretreatment, the 5‐HT content of the adult and 1‐day‐old rat brain increased to 2–3 times the control level and that of the supernatant fraction to about 40% of the 5‐HT content of the total homogenate. The adult values for 5‐HT in the particulate fraction of the 1‐day‐old rats after the drug treatments are in sharp contradiction to the low endogenous 5‐HT content and known lack of nerve terminals and synaptic vesicles in their brains, and suggest that after MAO inhibition brain 5‐HT neurons may bind the amine by some other mechanism than the Mg2+‐ATP‐dependent, reserpine‐sensitive granular storage.