Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

Abstract

Abstract. In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na+/H + antiport, amiloride (1 mM) and ethylisopropylamiloride (EIPA, 50 ~tM), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na+]e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 gM). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the de novo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloridesensitive transport process, presumably the Na +/H + exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.

Endothelial cells modulate renin secretion from isolated mouse juxtaglomerular cells.

“…We then examined whether EC exerted a basal influence on spontaneous and stim- ulated renin secretion. Stimulation of renin secretion was achieved along three different pathways, namely via adenylate cyclase stimulation by forskolin (10MAM) and isoproterenol (10 MM) (4), via inhibition of calmodulin activity by calmidazolium (10MM) (4) and via inhibition ofsodium-proton exchange by ethylisopropylamiloride (10 and 50MuM) and by NH4C1 (18). As shown in Fig.…”

Stimulation of Renin Secretion by Angiotensin II Blockade is Gsα-Dependent

“…1,2 Angiotensin II inhibits renin release in kidney slices 3 and in isolated juxtaglomerular granular (JG) cells, where the effect is blocked by losartan. 4,5 In the isolated JG cell, angiotensin II increases intracellular calcium levels, with increases correlating with the reduction of renin release. 5 On the other hand, it is unclear whether the stimulatory arm of the short feedback loop (i.e., the increase of renin in response to a reduction of angiotensin II) can be explained by the reverse of the same mechanism.…”

Blockade of ENaCs by amiloride induces c-Fos activation of the area postrema

“…Finally, since the renin is released from the kidney following amiloride treatment (Kurtz et al, 1991), there is a possibility that this hormone played a role in inducing c-Fos activity in the CVOs. Additional evidence suggests that the renin-angiotensin system is operative in the CVOs (McKinley et al, 2003a; McKinley et al, 2003b) including the AP (Hindmarch et al, 2011), so this possibility needs further analysis.…”