Noda Y, Yamada K, Igic R, Erdös E G
Proc Natl Acad Sci U S A. 1983 May;80(10):3059-63. doi: 10.1073/pnas.80.10.3059.
Rats were adrenalectomized and injected for 7 days with dexamethasone (DEX) or deoxycorticosterone. Kallikrein and prekallikrein were assayed in urine and in a basolateral membrane-enriched fraction. The activities of renin and phospholipase A2 were also determined in the fraction. Adrenalectomy significantly decreased active kallikrein in urine. Administration of deoxycorticosterone raised the level of active kallikrein in urine without affecting the concentration of prekallikrein. Rats treated with DEX only had high Na+ and low active kallikrein excretion. The total kallikrein level (active kallikrein together with prekallikrein), however, returned to normal because DEX elevated the prekallikrein level. DEX also increased the prekallikrein concentration in the membrane-enriched fraction. Renin activity in the membrane-enriched fraction was enhanced by adrenalectomy but suppressed by either corticosteroid. The changes in the concentration of plasma renin were qualitatively similar but quantitatively different. The activity of phospholipase A2 in the membrane-enriched fraction was enhanced only by deoxycorticosterone. Thus, both gluco- and mineralocorticoids increased kallikrein excretion in the adrenalectomized animals, but DEX was apparently effective at a lower dose than deoxycorticosterone. DEX increases the prekallikrein concentration in urine and on the basal membrane of distal tubular cells and, in addition, may prevent its conversion by releasing an inhibitor of a prekallikrein activator.
将大鼠进行肾上腺切除,并注射地塞米松(DEX)或脱氧皮质酮7天。检测尿液和富含基底外侧膜的部分中的激肽释放酶和前激肽释放酶。还测定了该部分中肾素和磷脂酶A2的活性。肾上腺切除显著降低了尿液中活性激肽释放酶的水平。给予脱氧皮质酮可提高尿液中活性激肽释放酶的水平,而不影响前激肽释放酶的浓度。仅用DEX治疗的大鼠钠排泄高且活性激肽释放酶排泄低。然而,由于DEX提高了前激肽释放酶水平,总激肽释放酶水平(活性激肽释放酶与前激肽释放酶之和)恢复正常。DEX还增加了富含膜部分中的前激肽释放酶浓度。肾上腺切除可增强富含膜部分中的肾素活性,但两种皮质类固醇均可抑制该活性。血浆肾素浓度的变化在定性上相似但在定量上不同。仅脱氧皮质酮可增强富含膜部分中的磷脂酶A2活性。因此,糖皮质激素和盐皮质激素均可增加肾上腺切除动物的激肽释放酶排泄,但DEX在较低剂量时显然比脱氧皮质酮更有效。DEX增加尿液和远端肾小管细胞基底膜上的前激肽释放酶浓度,此外,可能通过释放前激肽释放酶激活剂的抑制剂来阻止其转化。