Effects of various anions on serotonin transport in human platelets

A survey is given of some results from the author's studies on serotonin (5HT) uptake in human blood platelets in vitro. These findings are relevant also for serotonin reuptake at serotonergic synapses, since it has been shown that the serotonin transporter (5HTT) in platelets is identical to that in the brain. The main findings: 5HT uptake is dependent on the presence of Cl-, which shows simple saturation kinetics in relation to 5HT uptake rate, probably by acting on a hypothetical "anion site". Chloride can, however, be partly replaced by other small anions like bromide, iodide and nitrite. Unexpectedly, increasing concentrations of nitrite gives a sigmoidal 5HT uptake curve, indicating a double effect: being able to replace chloride in the "anion site", and exerting an allosteric effect by being bound to a separate "activating site". It was later found that the monocarboxylic acids acetate, lactate and pyruvate, which can not replace chloride, have an allosteric stimulatory effect on 5HT uptake in the presence of chloride, presumably by acting at the same activating site as shown for nitrite. The chloride concentration, as well as lactate and puruvate, may exert a regulatory effect on serotonin reuptake in the brain.