Rius Maria, Thon Walter F, Keppler Dietrich, Nies Anne T
Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
J Urol. 2005 Dec;174(6):2409-14. doi: 10.1097/01.ju.0000180411.03808.cb.
The seminal vesicles are the major source of prostaglandins in seminal fluid. For prostanoid action on cell surfaces they must be released from synthesizing cells. MRP4/ABCC4 (multidrug resistance protein 4 adenosine triphosphate-binding cassette, subfamily C, member 4) is an adenosine triphosphate dependent export pump for organic anions that may mediate prostanoid transport across the plasma membranes. Therefore, we analyzed whether MRP4 is expressed in the seminal vesicles and other tissues of the human urogenital tract, whether MRP4 and prostanoid synthesizing enzymes are co-expressed in the same cell type and whether MRP4 functions as a prostanoid export pump.
The expression and localization of MRP4 and prostanoid synthesizing enzymes were investigated in several tissues of the male human urogenital tract by immunoblot and immunofluorescence analyses. Prostanoid transport was measured into inside-out membrane vesicles from cells expressing recombinant human MRP4.
MRP4 and prostanoid synthesizing enzymes were co-expressed in the epithelial cells of human seminal vesicles. Moreover, MRP4 was localized in the plasma membrane of epithelial cells of the ureter, in the basolateral membrane of glandular epithelial cells of the prostate, and in smooth muscle cells of the bladder and corpus cavernosum. Transport studies established MRP4 as an efflux pump for prostaglandin E2 (Michaelis constant [Km] 3.5 muM), thromboxane B2 (Km 9.9 muM) and prostaglandin F2alpha (Km 12.6 muM).
The co-expression of prostanoid synthesizing enzymes and MRP4 in epithelial cells of the human seminal vesicles and the function of MRP4 as a prostanoid efflux pump indicate that MRP4 mediates prostanoid transport from these cells, which are the main prostanoid synthesizing cells in the male urogenital tract.
精囊是精液中前列腺素的主要来源。前列腺素要作用于细胞表面，必须从合成细胞中释放出来。多药耐药蛋白4/ABCC4（多药耐药蛋白4，三磷酸腺苷结合盒，C亚家族，成员4）是一种依赖三磷酸腺苷的有机阴离子输出泵，可能介导前列腺素跨质膜的转运。因此，我们分析了MRP4在人类泌尿生殖道的精囊和其他组织中是否表达，MRP4与前列腺素合成酶是否在同一细胞类型中共表达，以及MRP4是否作为前列腺素输出泵发挥作用。
通过免疫印迹和免疫荧光分析，研究了MRP4和前列腺素合成酶在男性人类泌尿生殖道多个组织中的表达和定位。测定了重组人MRP4表达细胞的内翻膜囊泡对前列腺素的转运。
MRP4和前列腺素合成酶在人类精囊的上皮细胞中共表达。此外，MRP4定位于输尿管上皮细胞的质膜、前列腺腺上皮细胞的基底外侧膜以及膀胱和海绵体的平滑肌细胞中。转运研究证实MRP4是前列腺素E2（米氏常数[Km]3.5μM）、血栓素B2（Km 9.9μM）和前列腺素F2α（Km 12.6μM）的外排泵。
前列腺素合成酶与MRP4在人类精囊上皮细胞中的共表达以及MRP4作为前列腺素外排泵的功能表明，MRP4介导前列腺素从这些细胞中转运，而这些细胞是男性泌尿生殖道中主要的前列腺素合成细胞。
