6533b824fe1ef96bd1280015

RESEARCH PRODUCT

Characterisation of serotonin transport mechanisms in rainbow trout peripheral blood lymphocytes: role in PHA-induced lymphoproliferation

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Abstract AbstractIn this study we investigated the serotonin transport mechanisms in rainbow trout (Oncorhynchus mykiss) peripheral blood lymphocytes We have observed that the transport of serotonin is a membrane transport process that have the properties of a secondary active transport system The binding isotherm of [3H]-paroxetine a serotonin transport blocker demonstrated a high-affinity binding site with a positive type of cooperativity Hill coefficient being higher than unity Known specific inhibitors of the mammalian serotonin transporter significantly inhibited the uptake process in fish lymphocytes In order to demonstrate the physiological relevance of the serotonin transporter in T-cell activation we conducted experiments on lymphocytes activated or not by phytohemagglutinin (PHA) a T-cell mitogen We have observed that addition of PHA for 24 hrs increased the Vmax but not the Km of this transporter Serotonin uptake inhibitors diminished the PHA-activated proliferation of fish lymphocytes The intracellular concentrations of cAMP were found to regulate the serotonin uptake and the PHA-stimulated proliferation as the agents known to augment cAMP stimulated serotonin uptake and inhibited the lymphoproliferation Inhibitory effects of increased cAMP on the proliferation were reversed by the addition of the nanomolar concentrations of 8-OH-DPAT a 5-HT1A receptor agonist which is known to diminish the intracellular cAMP concentrations suggesting that serotonin also regulates PHA-induced proliferation via 5-HT1A membrane receptors in an autocrine manner These results all together demonstrate that fish lymphocytes possess an active serotonin transporter that is implicated in the proliferation of these immunocompetent cells © 1999 Elsevier Science Ltd All rights reserved