Groves Carlotta E, Suhre Wendy B, Cherrington Nathan J, Wright Stephen H
Department of Physiology, University of Arizona, Tucson, 85724, USA.
J Pharmacol Exp Ther. 2006 Feb;316(2):743-52. doi: 10.1124/jpet.105.094979. Epub 2005 Oct 25.
Sex differences in transport of the organic anion (OA) substrate p-aminohippurate (PAH) and the organic cation (OC) substrate tetraethylammonium (TEA) have been recognized for some time. In the rat kidney, androgens up-regulate and estrogens down-regulate PAH and TEA transport, which correlate with similar changes in mRNA and protein expression for the renal basolateral membrane transporters organic anion transporter (Oat) 1 and organic cation transporter (Oct) 2. However, these sex differences are not readily demonstrated in other species. The present study characterizes the kinetics of basolateral membrane PAH, estrone sulfate (ES), and TEA uptake in renal proximal tubule (RPT) suspensions isolated from female and male rabbits to compare functional expression of transport with mRNA and protein expression for rbOat1, rbOat3, and rbOct2. Although rbOat1-rbOat3 mRNA expression exhibited developmental differences, no sex differences in mRNA levels were observed. Oat1 and Oat3 protein expression in RPT suspensions also was similar between adult female and male rabbits. In contrast, rbOct1 and rbOct2 mRNA levels did not show developmental differences, but rbOct2 mRNA expression was greater in adult male than female rabbits. However, the sex difference in rbOct2 mRNA level did not translate to rbOct2 protein expression. Importantly, functional expression of Oat1, Oat3, and Oct2 transport as measured by kinetics (J(max) and K(t)) of PAH, ES, and TEA uptake was similar between adult male and female rabbits, and correlated with rbOat1, rbOat3, and rbOct2 protein expression. Thus, unlike rodents, rabbit renal OA and OC transport does not exhibit sex differences, pointing to the need for caution in extrapolating transport-related sex differences between species.
有机阴离子（OA）底物对氨基马尿酸（PAH）和有机阳离子（OC）底物四乙铵（TEA）转运过程中的性别差异已被认识有一段时间了。在大鼠肾脏中，雄激素上调而雌激素下调PAH和TEA的转运，这与肾基底外侧膜转运蛋白有机阴离子转运体（Oat）1和有机阳离子转运体（Oct）2的mRNA和蛋白质表达的类似变化相关。然而，这些性别差异在其他物种中并不容易表现出来。本研究对从雌性和雄性兔分离的肾近端小管（RPT）悬浮液中基底外侧膜PAH、硫酸雌酮（ES）和TEA摄取的动力学进行了表征，以比较转运的功能表达与rbOat1、rbOat3和rbOct2的mRNA和蛋白质表达。尽管rbOat1 - rbOat3的mRNA表达存在发育差异，但未观察到mRNA水平的性别差异。成年雌性和雄性兔的RPT悬浮液中Oat1和Oat3的蛋白质表达也相似。相比之下，rbOct1和rbOct2的mRNA水平没有显示出发育差异，但成年雄性兔的rbOct2 mRNA表达高于雌性兔。然而，rbOct2 mRNA水平的性别差异并未转化为rbOct2蛋白质表达。重要的是，通过PAH、ES和TEA摄取的动力学（J(max)和K(t)）测量的Oat1、Oat3和Oct2转运的功能表达在成年雄性和雌性兔之间相似，并且与rbOat1、rbOat3和rbOct2的蛋白质表达相关。因此，与啮齿动物不同，兔肾OA和OC转运不存在性别差异，这表明在推断物种间与转运相关的性别差异时需要谨慎。
