Serotonin transporter kinetics in rats selected for extreme values of platelet serotonin level

Abstract

By selective breeding of Wistar rats for the extreme values of platelet serotonin (5HT) level (PSL), we have developed earlier two sublines of animals differing markedly in this parameter. Further studies, performed on the protein and mRNA levels, revealed platelet serotonin transporter (5HTt) as parameter underlying mentioned differences in PSL between sublines. In this work, we have performed full-kinetic analysis of platelet serotonin uptake (PSU) in animals from the genetically selected sublines. The results demonstrated marked differences in maximal velocity (V(max)) of the 5HT transporter, as contrasted to the lack of any difference in the Michaelis constant (K(m)). High correlation between PSL and V(max) of PSU was demonstrated, revealing that the number of membrane 5HT transporter sites is under genetic control and responsible for marked differences in PSL between high- and low-5HT sublines. These results enabled further selective breeding of animals for the extremes of V(max) of platelet 5HT transporter, and so the development of more specific model "Wistar-Zagreb 5HT rats".