Rebuffat P, Mazzocchi G, Macchi C, Malendowicz L K, Gottardo G, Nussdorfer G G
Department of Anatomy, University of Padua, I-35121 Padua, Italy.
Int J Mol Med. 1999 Mar;3(3):307-10. doi: 10.3892/ijmm.3.3.307.
Endothelin (ET)-1 is the prototype of a family of 21-amino acid residue hypertensive peptides, acting through two subtypes of receptors, named ETA and ETB. ETs and their receptors are expressed in the adrenal cortex and medulla, and ET-1 enhances both corticosteroid and catecholamine release. ET-1 concentration-dependently (from 10(-11) to 10(-8) M) increased aldosterone secretion of both dispersed rat zona glomerulosa (ZG) cells and adrenal slices containing a core of medullary chromaffin tissue, but the response of the latter preparations was significantly more intense than that of the formers. The stimulatory effect of 10(-8) M ET-1 on dispersed ZG cells was blocked by the ETB-receptor antagonist BQ-788 (10(-7) M), but not by the ETA-receptor antagonist BQ-123 (10(-7) M); conversely, both ET-receptors antagonists counteracted aldosterone response of adrenal slices to ET-1. The -adrenoceptor antagonist l-alprenolol (10(-6) M) did not affect aldosterone response of dispersed ZG cells to ET-1 (10(-8) M), but it significantly lowered that of adrenal slices. l-Alprenolol also counteracted the aldosterone response of adrenal slices to the pure activation of ETB or ETA receptors, as obtained by using the selective ETB-receptor agonist BQ-3020 (10(-8) M) or ET-1 (10(-8) M) plus BQ-788 (10(-7) M). ET-1 concentration-dependently (from 10(-9) to 10(-8)/10(-7) M) stimulated catecholamine release by adrenal slices, and the effect was counteracted by both BQ-123 and BQ-788 (10(-7) M). Collectively, our findings suggest that, when the integrity of adrenal tissue is preserved, a two-fold mechanism underlies the aldosterone secretagogue action of ET-1 in the rat: i) a direct mechanism mediated by ETB receptors located on ZG cells; and ii) an indirect mechanism involving the ETA and ETB receptor-mediated local release of catecholamines, which in turn stimulate ZG cells in a paracrine manner.
内皮素（ET）-1是一种由21个氨基酸残基组成的高血压肽家族的原型，通过两种受体亚型（称为ETA和ETB）发挥作用。ET及其受体在肾上腺皮质和髓质中表达，ET-1可增强皮质类固醇和儿茶酚胺的释放。ET-1浓度依赖性地（从10^(-11)到10^(-8)M）增加了分散的大鼠肾小球带（ZG）细胞和含有髓质嗜铬组织核心的肾上腺切片的醛固酮分泌，但后者制剂的反应明显比前者强烈。10^(-8)M的ET-1对分散的ZG细胞的刺激作用被ETB受体拮抗剂BQ-788（10^(-7)M）阻断，但不被ETA受体拮抗剂BQ-123（10^(-7)M）阻断；相反，两种ET受体拮抗剂都抵消了肾上腺切片对ET-1的醛固酮反应。β-肾上腺素能受体拮抗剂l-阿普洛尔（10^(-6)M）不影响分散的ZG细胞对ET-1（10^(-8)M）的醛固酮反应，但它显著降低了肾上腺切片的反应。l-阿普洛尔还抵消了肾上腺切片对ETB或ETA受体纯激活的醛固酮反应，这是通过使用选择性ETB受体激动剂BQ-3020（10^(-8)M）或ET-1（10^(-8)M）加BQ-788（10^(-7)M）获得的。ET-1浓度依赖性地（从10^(-9)到10^(-8)/10^(-7)M）刺激肾上腺切片释放儿茶酚胺，并且该作用被BQ-123和BQ-788（10^(-7)M）抵消。总的来说，我们的研究结果表明，当肾上腺组织的完整性得以保留时，ET-1在大鼠中醛固酮促分泌作用的机制有两方面：i）由ZG细胞上的ETB受体介导的直接机制；ii）涉及ETA和ETB受体介导的儿茶酚胺局部释放的间接机制，儿茶酚胺进而以旁分泌方式刺激ZG细胞。
