Limas C, Limas C J
Laboratory Service, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Arch Biochem Biophys. 1987 Nov 15;259(1):89-97. doi: 10.1016/0003-9861(87)90473-5.
Prostaglandin (PG) receptors are present on enzymatically dissociated cells from the rat renal medulla and are subject to homologous regulation both in vivo and in vitro. One hour after injection of 100 micrograms of 16,16'-dimethyl-PGE2, the number of PGE2 binding sites on renal cells declines to 40% of controls. In vitro exposure of renal cells to PGE2 or dimethyl-PGE2 also results in a time- and concentration-dependent "down" regulation of prostaglandin receptors. In the absence of indomethacin in the incubation medium, endogenously synthesized prostaglandins mediate a similar time-dependent loss of cell-associated receptors. This loss is reversible since, after agonist removal and reincubation of the cells at 37 degrees C, there is a rapid (within 15 min) reappearance of PGE2 receptors (to 60-93% of controls). Reappearance occurs whether down regulation is induced in vitro by endogenously synthesized prostaglandins, added PGE2 or dimethyl-PGE2, or in vivo after injection of dimethyl-PGE2. Cycloheximide does not affect down regulation but significantly prevents subsequent recovery of the receptors. In contrast, neither colchicine nor chloroquine influences homologous regulation of renal prostaglandin receptors. These results document an agonist-induced reversible cycling of renal prostaglandin receptors which may determine the effectiveness of prostaglandin action in normal and pathologic states.
前列腺素（PG）受体存在于从大鼠肾髓质酶解分离的细胞上，且在体内和体外均受到同源调节。注射100微克16,16'-二甲基-PGE2 1小时后，肾细胞上PGE2结合位点的数量降至对照的40%。肾细胞在体外暴露于PGE2或二甲基-PGE2也会导致前列腺素受体出现时间和浓度依赖性的“下调”。在孵育培养基中不存在吲哚美辛的情况下，内源性合成的前列腺素介导细胞相关受体出现类似的时间依赖性丧失。这种丧失是可逆的，因为在去除激动剂并将细胞在37℃下重新孵育后，PGE2受体迅速（15分钟内）重新出现（达到对照的60 - 93%）。无论下调是由内源性合成的前列腺素、添加的PGE2或二甲基-PGE2在体外诱导，还是在注射二甲基-PGE2后在体内诱导，都会出现重新出现的情况。放线菌酮不影响下调，但显著阻止受体随后的恢复。相比之下，秋水仙碱和氯喹均不影响肾前列腺素受体的同源调节。这些结果证明了激动剂诱导的肾前列腺素受体可逆循环，这可能决定了前列腺素在正常和病理状态下作用的有效性。
