Craven P A, DeRubertis F R
Metabolism. 1985 Jul;34(7):651-7. doi: 10.1016/0026-0495(85)90093-9.
This study examined the role of cGMP in the control of renin release from isolated rat glomeruli. An inverse correlation between renin release and cGMP content of isolated glomeruli was found under several conditions of incubation. Thus, incubation of isolated glomeruli in Ca2+-free media containing EGTA, or the addition of the Ca2+ and calmodulin (CaM) antagonists trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W-7), or (8-N, N-diethylamino)-octyl 3,4,5-trimethoxybenzoate-HCI (TMB-8) to glomeruli incubated in Ca2+ replete buffer lowers cGMP and stimulates renin release. These same incubation conditions enhance the release of renin induced by isoproterenol (DBcAMP) in isolated glomeruli. By contrast, raising media K+ to 60 mmol/L, or the incubation of glomeruli with angiotensin II (A-II) or ouabain--all of which are thought to increase intracellular Ca2+--increased glomerular cGMP and suppressed basal glomerular renin release and the increases in renin release induced by isoproterenol (DBcAMP). However, neither exogenous DBcAMP nor nitroprusside, an agent that increased the endogenous cGMP, content of glomeruli mimicked the suppressive effects of high K+, A-II, or ouabain on renin release. Moreover, DBcGMP and nitroprusside also failed to reverse the stimulatory effects of Ca2+ deprivation, TFP, W-7, or TMB-8 on glomerular renin release, even though nitroprusside clearly enhanced cGMP under these conditions of incubation. The results suggest that changes in glomerular cGMP and renin release occur concomitantly in response to alterations in glomerular Ca2+ homeostasis, but that cGMP does not mediate the changes in glomerular renin release.
本研究探讨了环磷酸鸟苷（cGMP）在调控离体大鼠肾小球肾素释放中的作用。在几种孵育条件下，发现肾素释放与离体肾小球的cGMP含量呈负相关。因此，将离体肾小球置于含乙二醇双（2-氨基乙醚）四乙酸（EGTA）的无钙培养基中孵育，或向在含钙充足缓冲液中孵育的肾小球添加钙（Ca2+）和钙调蛋白（CaM）拮抗剂三氟拉嗪（TFP）、N-（6-氨基己基）-5-氯-1-萘磺酰胺盐酸盐（W-7）或（8-N，N-二乙氨基）-辛基3,4,5-三甲氧基苯甲酸盐酸盐（TMB-8），可降低cGMP并刺激肾素释放。这些相同的孵育条件可增强异丙肾上腺素（二丁酰环磷腺苷，DBcAMP）在离体肾小球中诱导的肾素释放。相比之下，将培养基钾离子（K+）浓度提高到60 mmol/L，或将肾小球与血管紧张素II（A-II）或哇巴因一起孵育（所有这些都被认为会增加细胞内Ca2+），会增加肾小球cGMP并抑制基础肾小球肾素释放以及异丙肾上腺素（DBcAMP）诱导的肾素释放增加。然而，外源性DBcAMP或硝普钠（一种增加肾小球内源性cGMP含量的药物）均未模拟高钾、A-II或哇巴因对肾素释放的抑制作用。此外，尽管硝普钠在这些孵育条件下明显提高了cGMP，但双丁酰环磷鸟苷（DBcGMP）和硝普钠也未能逆转钙离子剥夺、TFP、W-7或TMB-8对肾小球肾素释放的刺激作用。结果表明，肾小球cGMP和肾素释放的变化是伴随肾小球Ca2+稳态改变而发生的，但cGMP并不介导肾小球肾素释放的变化。
