Massry S G, Klin M, Ni Z, Tian J, Kedes L, Smogorzewski M
Department of Medicine, University of Southern California, School of Medicine, Los Angeles, USA.
Kidney Int. 1995 Oct;48(4):1324-31. doi: 10.1038/ki.1995.417.
Some hormones exert their action by inducing a rise in cytosolic calcium [Ca2+]i (calcium signal), and therefore, a blunting in hormone-induced calcium signal would engender resistance to the action of the hormone. Chronic renal failure (CRF) is associated with resistance to the action of a variety of hormones, a rise in [Ca2+]i and decrease in the amount of mRNA of one hormone receptor, the PTH-PTHrP receptor. We examined the calcium-signal induced by PTH, angiotensin II, vasopressin and glucagon in hepatocytes from CRF animals, evaluated the effect of the basal level [Ca2+]i on the calcium signal and explored the effect of [Ca2+]i on the mRNA of the receptors of these agonists. Hepatocytes from CRF rats have elevated basal levels of [Ca2+]i and display significantly reduced calcium signals induced by all these hormones, while the calcium signals were normal in PTX-CRF animals and those treated with verapamil both of which have normal levels of [Ca2+]i despite CRF. The calcium signals induced by dibutyryl cyclic AMP and G protein activator (GTP gamma S) were normal in hepatocytes from CRF animals despite the high levels of [Ca2+]i. Northern blotting experiments revealed that the levels of the mRNA of the receptors of PTH-PTHrP, angiotensin II and vasopressin were significantly reduced in hepatocytes from CRF animals but PTX-CRF rats and those treated with verapamil had either significantly greater or even normal amounts of the mRNA of these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
一些激素通过诱导胞质钙[Ca2+]i升高（钙信号）来发挥作用，因此，激素诱导的钙信号减弱会导致对该激素作用产生抵抗。慢性肾衰竭（CRF）与多种激素作用抵抗、[Ca2+]i升高以及一种激素受体——甲状旁腺激素-甲状旁腺激素相关蛋白（PTH-PTHrP）受体的mRNA量减少有关。我们检测了CRF动物肝细胞中由甲状旁腺激素（PTH）、血管紧张素II、血管加压素和胰高血糖素诱导的钙信号，评估了基础水平[Ca2+]i对钙信号的影响，并探究了[Ca2+]i对这些激动剂受体mRNA的影响。CRF大鼠的肝细胞基础[Ca2+]i水平升高，且所有这些激素诱导的钙信号显著降低，而在PTX-CRF动物以及用维拉帕米治疗的动物中，尽管存在CRF，但[Ca2+]i水平正常，其钙信号也正常。尽管[Ca2+]i水平较高，但CRF动物肝细胞中由二丁酰环磷酸腺苷（dibutyryl cyclic AMP）和G蛋白激活剂（GTPγS）诱导的钙信号正常。Northern印迹实验显示，CRF动物肝细胞中PTH-PTHrP、血管紧张素II和血管加压素受体的mRNA水平显著降低，但PTX-CRF大鼠以及用维拉帕米治疗的大鼠这些受体的mRNA量显著增加甚至正常。（摘要截短于250词）
