Читать книгу Drug Transporters - Группа авторов - Страница 40

Like hOCT1, the activity of human OCT2 can be regulated by protein kinase pathways. PKA stimulation inhibits the uptake of ASP⁺ by OCT2 expressing cells and the activation of PKC inhibits the basolateral ASP⁺ uptake in human proximal tubules [2]. hOCT2 is also inhibited by PI3K and activated by a CaM‐dependent signaling pathway, probably via a change in substrate affinity [2]. Moreover, tyrosine kinase inhibitors inhibit the Src family kinase Yes1, which was found to be essential for OCT2 tyrosine phosphorylation and function [2]. In addition, the expression of OCT2 can be regulated by sex hormones. Treatment of male and female rats with testosterone significantly increases the expression levels of rOCT2 mRNA and protein in the kidney, whereas estradiol treatment moderately decreases the expression levels of rOCT2. In accordance with increased OCT2 expression, treatment with testosterone significantly stimulates the TEA accumulation by renal slices in rats of both sexes, whereas estradiol treatment causes a decrease in the TEA accumulation by slices from male, but not female rats [41].