Massicotte G, Coderre L, Chiasson J L, Thibault G, Schiffrin E L, St-Louis J
Experimental Hypertension Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Am J Physiol. 1990 Apr;258(4 Pt 1):E597-605. doi: 10.1152/ajpendo.1990.258.4.E597.
Recent evidence suggests that angiotensin II (ANG II) and vasopressin (AVP) act on the liver via specific receptors. We have examined the binding properties of these receptors in isolated rat hepatocytes and studied the regulation of the biological responses to ANG II and AVP during pregnancy in the rat. In contrast to [3H]ANG II, 125I-labeled-[Sar1-Ile8]ANG II was markedly resistant to degradation by isolated liver cells. Displacement and saturation experiments with this iodinated antagonist revealed the presence of a single class of binding sites [2 x 10(5) sites/cell, dissociation constant (KD) = 1.0 nM]. The potency of ANG II analogues to displace 125I-[Sar1-Ile8]-ANG II agrees closely with data reported for vascular smooth muscle cells. Isolated hepatocytes have approximately 8 x 10(4) [3H]AVP binding sites/cell (KD = 1.0 nM) based on saturation experiments. AVP analogues selectively displaced [3H]AVP, suggesting the presence of V1-AVP receptor subtype. The maximum response of [Sar1]ANG II-induced glycogenolysis in the cells was decreased during gestation, whereas the effective concentration producing 50% of maximum response (EC50) was significantly increased (0.15-0.28 nM) when compared with cells from nonpregnant animals. In pregnancy, receptors for 125I-[Sar1-Ile8]ANG II were not changed in affinity (KD) or in density (Bmax). The maximum response and EC50 of AVP on liver glycogenolysis were not significantly decreased during pregnancy, whereas an increased number of AVP binding sites (from 5.0 +/- 0.5 x 10(4) to 11.0 +/- 1.7 x 10(4)) with similar KD was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
近期证据表明，血管紧张素II（ANG II）和血管加压素（AVP）通过特定受体作用于肝脏。我们研究了这些受体在分离的大鼠肝细胞中的结合特性，并探讨了大鼠孕期对ANG II和AVP生物学反应的调节。与[3H]ANG II不同，125I标记的-[Sar1-Ile8]ANG II对分离的肝细胞降解具有显著抗性。用这种碘化拮抗剂进行的置换和饱和实验显示存在一类单一的结合位点[2×10(5)个位点/细胞，解离常数（KD）=1.0 nM]。ANG II类似物置换125I-[Sar1-Ile8]-ANG II的效力与报道的血管平滑肌细胞数据密切相符。基于饱和实验，分离的肝细胞约有8×1(4)个[3H]AVP结合位点/细胞（KD = 1.0 nM）。AVP类似物选择性地置换[3H]AVP，提示存在V1-AVP受体亚型。孕期细胞中[Sar1]ANG II诱导糖原分解的最大反应降低，而与未孕动物细胞相比，产生最大反应50%的有效浓度（EC50）显著增加（0.15 - 0.28 nM）。孕期，125I-[Sar1-Ile8]ANG II受体的亲和力（KD）和密度（Bmax）未改变。孕期AVP对肝脏糖原分解的最大反应和EC50未显著降低，而观察到AVP结合位点数量增加（从5.0±0.5×10(4)增加到11.0±1.7×10(4)），KD相似。（摘要截断于250字）
