Uptake resolved by high-speed chronoamperometry on a second-by-second basis has revealed important differences in brain serotonin transporter function associated with genetic variability. Here, we use chronoamperometry to investigate variations in serotonin transport in primary lymphocytes associated with the rhesus serotonin transporter gene-linked polymorphism (rh5-HTTLPR), a promoter polymorphism whose orthologs occur only in higher order primates including humans. Serotonin clearance by lymphocytes is Na(+)-dependent and inhibited by the serotonin-selective reuptake inhibitor paroxetine (Paxil(R)), indicative of active uptake by serotonin transporters. Moreover, reductions in serotonin uptake rates are evident in lymphocytes from monkeys with one or two copies of the short 's' allele of the rh5-HTTLPR (s/s<s/l<l/l). These findings illustrate that rh5-HTTLPR-related alterations in serotonin uptake are present during adulthood in peripheral blood cells natively expressing serotonin transporters. Moreover, they suggest that lymphocytes can be used as peripheral biomarkers for investigating genetic or pharmacologic alterations in serotonin transporter function. Use of boron-doped diamond microelectrodes for measuring serotonin uptake, in contrast to carbon fiber microelectrodes used previously in the brain, enabled these high-sensitivity and high-resolution measurements. Boron-doped diamond microelectrodes show excellent signal-to-noise and signal-to-background ratios due mainly to low background currents and are highly resistant to fouling when exposed to lymphocytes or high concentrations of serotonin.
- Serotonin transporter
- promoter polymorphism
- nonhuman primate
- peripheral blood mononuclear cells
- carbon fiber microelectrode