Ackermann M, Ritthaler T, Riegger G, Kurtz A, Krämer B K
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S135-7.
We examined the effects of endothelin (ET)-1, -2, and -3 on renin secretion from cultured mouse renal juxtaglomerular cells. Although different ETs had no consistent effect on basal renin secretion, they equipotently inhibited cAMP-stimulated renin release with an IC50 value of approximately 3 nM. ETs did not significantly affect renin release stimulated by the nitric oxide (NO)-donor nitroprusside (100 microM) or that stimulated by low (2 mM EGTA) or high (3 mM CaCl2) extracellular calcium. The inhibitory effect of ETs on cAMP-dependent renin secretion was abolished by lowering extracellular calcium concentration to the nanomolar range. However, the action of ETs was not changed by the ETA receptor antagonist BQ 123 (100 nM) and was mimicked by the ETB receptor agonists IRL 1620 (1 microM), sarafotoxin S6c (1 microM), and [Ala1,3,11,15]endothelin-1 (4 Ala-ET-1, 1 microM). These findings suggest that ETs selectively inhibit the cAMP-activated pathway of renin secretion through a calcium-sensitive process. The action of ETs on renal juxtaglomerular cells appears to be mediated via ETB receptors.
我们研究了内皮素（ET）-1、-2和-3对培养的小鼠肾近球细胞肾素分泌的影响。尽管不同的内皮素对基础肾素分泌没有一致的作用，但它们能以约3 nM的半数抑制浓度（IC50）同等程度地抑制环磷酸腺苷（cAMP）刺激的肾素释放。内皮素对一氧化氮（NO）供体硝普钠（100 μM）刺激的肾素释放或细胞外低钙（2 mM乙二醇双四乙酸）或高钙（3 mM氯化钙）刺激的肾素释放均无显著影响。将细胞外钙浓度降至纳摩尔范围可消除内皮素对cAMP依赖性肾素分泌的抑制作用。然而，内皮素受体拮抗剂BQ 123（100 nM）并未改变内皮素的作用，而内皮素B（ETB）受体激动剂IRL 1620（1 μM）、芋螺毒素S6c（1 μM）和[丙氨酸1,3,11,15]内皮素-1（4 Ala-ET-1，1 μM）可模拟其作用。这些发现表明，内皮素通过钙敏感过程选择性抑制肾素分泌的cAMP激活途径。内皮素对肾近球细胞的作用似乎是通过ETB受体介导的。
