engleski

Central aminopeptidase and serotonin system activities : possible relationship

Co-localization of serotonin (5-hydroxytryptamine, 5HT) and neuroactive peptides in the same neuron points to the importance of interactions between serotonergic and peptidergic systems in maintaing body homeostasis. In this work we used an original genetic rat model to search for possible interrelations between 5HT system functioning and activities of aminopeptidases, i.e. enzymes which are key regulators of (neuro)peptides level/function. Activities of three cytosolic exopeptidases: alanyl aminopeptidase (alanyl AP), arginyl aminopeptidase (arginyl AP) and dipeptidyl peptidase III (DPP III) were measured in brains and peripheral tissues of sublines of rats with constitutionally upregulated/downregulated 5HT transporter activity. These rat sublines, termed high-5HT and low-5HT subline, have been obtained previously by selective breeding for the extreme values of platelet 5HT level and velocity of 5HT uptake. Beside in the periphery they show marked alterations also in brain 5HT function, indicating differences in central 5HT transmission/homeostasis. In this study we have found that animals from the high-5HT subline have significantly lower activity of brain alanyl-AP (p<0.05) and arginyl-AP (p<0.01) as compared to control animals. No other differences were noticed regardless the 5HT-subline, investigated organ or aminopeptidase analyzed. Results suggest that constitutional upregulation of serotonergic activity may be related to lowered brain cytosolic aminopeptidase activity which may have influence on cleavage of their physiological substrates.

serotonin; rat brain; exopeptidases

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