Calcium in the control of renin secretion: Ca2+ influx as an inhibitory signal

1981 ◽  
Vol 240 (1) ◽  
pp. F70-F74 ◽  
Author(s):  
C. S. Park ◽  
D. S. Han ◽  
J. C. Fray
Keyword(s):  
Incubation Temperature ◽  
Inhibitory Effect ◽  
Renin Secretion ◽  
Juxtaglomerular Cells ◽  
Stimulatory Action ◽  
Inhibitory Signal ◽  
Ca Antagonist ◽  
K Concentration ◽  
Energy Dependent

The mechanism for the inhibition of renin secretion in vitro from renal cortical slices by angiotensin II, antidiuretic hormone, ouabain, and high K+ concentration was studied. The inhibitory effect of these agents was blocked by a Ca antagonist, verapamil. In addition, epinephrine stimulated renin secretion and its stimulatory action was blocked by ouabain. These results support the hypothesis that Ca2+ influx into juxtaglomerular cells plays a role as an inhibitory signal whereas Ca2+ efflux is a stimulatory signal for renin secretion. Renin secretion was greatly stimulated by lowering incubation temperature, indicating that renin secretion is not energy dependent. The possibility is discussed that Ca2+ of juxtaglomerular cells might activate an enzyme(s) that then modulates some sequential steps of renin secretory processes, thereby controlling the rate of renin secretion.

Stimulatory action of parathyroid hormone on renin secretion in vitro: a study using isolated rat kidney, isolated rabbit glomeruli and superfused dispersed rat juxtaglomerular cells

1993 ◽  
Vol 84 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Christian Saussine ◽  
C. Judes ◽  
T. Massfelder ◽  
M.-J. Musso ◽  
U. Simeoni ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Rat Kidney ◽  
Renin Secretion ◽  
Renin Release ◽  
Juxtaglomerular Cells ◽  
Isolated Kidney ◽  
Stimulatory Action ◽  
Isolated Rat Kidney ◽  
Isolated Rat

1. We have previously reported that pharmacological concentrations (125 nmol/l) of parathyroid hormone may stimulate renin release in the stable recirculating and non-filtering isolated rat kidney. 2. In the present study we have attempted to extend these initial observations by examining the concentration-related response of renin release to parathyroid hormone, using the same model of isolated kidney, and determining whether the effect of parathyroid hormone on renin release can be demonstrated by more direct approaches. Thus, the effects of parathyroid hormone on renin secretion were investigated in two other renal preparations: isolated rabbit glomeruli and isolated rat juxtaglomerular cells. 3. In the isolated kidney, rat parathyroid hormone significantly stimulated renin accumulation in the perfusate in a concentration-related manner with a threshold of 1 nmol/l. 4. In both glomeruli and juxtaglomerular cells bovine [Nle8,18,Tyr34]parathyroid hormone-(1–34)amide effectively and repeatedly stimulated renin release. These results imply that there is a direct stimulatory effect of parathyroid hormone on renin release. 5. We also examined the effect of [Nle8,18, Tyr34]parathyroid hormone-(l-34)amide during extracellular calcium buffering in the glomeruli. [Nle8,18,Tyr34]parathyroid hormone-(1–34)amide was uneffective in calcium-free medium. Increasing the extracellular ionized calcium concentration to 2.5 mmol/l increased the extent of stimulation in accordance with the reported ability of parathyroid hormone to block calcium channels and relax vascular smooth muscle cells. 6. These results provide further support for the role of parathyroid hormone as a direct mediator of renin secretion; moreover, the renin-stimulating action of parathyroid hormone may be mediated through the inhibition of calcium influx.s

scholarly journals Effects of 2-mercaptoacetate in isolated liver mitochondria in vitro. Competitive inhibition of 3-hydroxybutyrate dehydrogenase and depression of the β-oxidation pathway

1982 ◽  
Vol 206 (1) ◽  
pp. 53-59 ◽  
Author(s):  
F Bauché ◽  
D Sabourault ◽  
Y Giudicelli ◽  
J Nordmann ◽  
R Nordmann
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Competitive Inhibition ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Acid Oxidation ◽  
Membrane Bound ◽  
Energy Dependent ◽  
Isolated Liver

The effects of 2-mercaptoacetate on the respiration rates induced by different substrates were studied in vitro in isolated liver mitochondria. With palmitoyl-L-carnitine or 2-oxoglutarate as the substrate, the ADP-stimulated respiration (State 3) was dose-dependently inhibited by 2-mercaptoacetate. with glutamate or succinate as the substrate. State-3 respiration was only slightly inhibited by 2-mercaptoacetate. In contrast, the oxidation rate of 3-hydroxybutyrate was competitively inhibited by 2-mercaptoacetate in both isolated mitochondria and submitochondrial particles. In uncoupled mitochondria and in mitochondria in which ATP- and GTP-dependent acyl-CoA biosynthesis was inhibited, the inhibitory effect of 2-mercaptoacetate on palmitoyl-L-carnitine oxidation was abolished; under the same conditions, however, inhibition of 3-hydroxybutyrate oxidation by 2-mercaptoacetate still persisted. These results led to the following conclusions: 2-mercaptoacetate itself enters the mitochondrial matrix, inhibits fatty acid oxidation through a mechanism requiring an energy-dependent activation of 2-mercaptoacetate and itself inhibits 3-hydroxybutyrate oxidation through a competitive inhibition of the membrane-bound 3-hydroxybutyrate dehydrogenase. This study also strongly suggests that the compound responsible for the inhibition of fatty acid oxidation is 2-mercaptoacetyl-CoA.

EFFECTS OF HYDROXYSTEROID DEHYDROGENASE INHIBITORS ON IN-VITRO AND IN-VIVO STEROIDOGENESIS IN THE OVINE ADRENAL GLAND

1982 ◽  
Vol 92 (2) ◽  
pp. 205-212 ◽  
Author(s):  
P. SINGH-ASA ◽  
G. JENKIN ◽  
G. D. THORBURN
Keyword(s):  
Adrenal Gland ◽  
Incubation Medium ◽  
Bovine Serum ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effect ◽  
Bovine Serum Albu ◽  
Stimulatory Action ◽  
Adrenal Steroidogenesis

The effectiveness of trilostane and azastene as inhibitors of adrenal steroidogenesis was compared by in-vitro and in-vivo methods. A radioimmunoassay was developed for the measurement of cortisol in ovine plasma, incubation medium and tissue extract using a specific antiserum raised against cortisol 21-acetate,3-carboxymethyloxime : bovine serum albu Trilostane (20 μmol/l) decreased cortisol synthesis and release both in unstimulated and in ACTH-stimulated adrenal tissues in vitro. The same concentration of azastene had a lesser effect on unstimulated adrenals and was completely ineffective in blocking the stimulatory action of ACTH. In vivo, trilostane suppressed adrenal steroidogenesis in pregnant and cyclic ewes but the suppression in pregnant ewes was over a longer period, and after lower doses. It is concluded that trilostane had an inhibitory effect on ovine adrenal steroidogenesis both in vitro and in vivo.

Stimulation of renin secretion by ethacrynic acid is independent of Na(+)-K(+)-2Cl- cotransport

1990 ◽  
Vol 259 (4) ◽  
pp. F539-F544 ◽  
Author(s):  
C. S. Park ◽  
P. S. Doh ◽  
R. E. Carraway ◽  
G. G. Chung ◽  
J. C. Fray ◽  
...  
Keyword(s):  
Loop Diuretic ◽  
Ethacrynic Acid ◽  
Inhibitory Effect ◽  
Renin Secretion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Specific Membrane ◽  
Cortical Slices ◽  
Stimulation Of

This study investigated the cellular mechanism of stimulation of renin secretion by the loop diuretic ethacrynic acid (EA) in rabbit renal cortical slices. The diuretic rapidly stimulated renin secretion reversibly and in a concentration-dependent manner. The stimulation was independent of the presence of Na+, Cl-, Ca2+, or other loop diuretics (furosemide and bumetanide) in the incubation media, suggesting that the stimulation in vitro was not dependent on the inhibitory effect of the diuretic on Na(+)-K(+)-2Cl-cotransport. The findings do not support the macula densa hypothesis. The stimulation by the diuretic was prevented and reversed by thiols such as cysteine and dithiothreitol, which also prevented and reversed the stimulation of renin secretion by the nondiuretic sulfhydryl reagent P-chloromercuriphenyl-sulfonate (PCMPS). These results suggest that EA stimulates renin secretion in vitro via reversible chemical reactions with specific membrane sulfhydryl groups that may have no functional role in the Na(+)-K(+)-2Cl- cotransport.

Regulation of in vitro renin secretion by ANG II feedback manipulation in vivo in the ovine fetus

1999 ◽  
Vol 277 (4) ◽  
pp. R1230-R1238 ◽  
Author(s):  
Carlos E. Giammattei ◽  
Jack W. Strandhoy ◽  
James C. Rose
Keyword(s):  
Feedback Regulation ◽  
Late Gestation ◽  
Renin Secretion ◽  
Juxtaglomerular Cells ◽  
Fetal Life ◽  
Ang Ii ◽  
Active Renin ◽  
Age Related

The renin-angiotensin system is critically important to fetal cardiovascular function and organ development. The feedback regulation of renin secretion by ANG II develops early in gestation yet does not linearly progress from fetal life to adulthood. Renin secretion is elevated in late gestation compared with earlier or postnatal time periods, which suggests that some component of the negative feedback regulation of renin secretion is less sensitive in late gestation. We examined in fetal sheep the age-related consequence of chronic in vivo manipulation of ANG II on renal renin secretion measured in vitro. Immature (101–103 days of gestation) and mature (130–133 days of gestation) fetuses were treated for 72 h with enalaprilat, ANG II or vehicle. Content and basal and isoproterenol-stimulated secretion of prorenin (PR) and active renin (AR) from fetal kidney cortical slices were determined. Enalaprilat pretreatment in vivo increased renal renin content and basal and stimulated secretion of PR and AR in vitro even in immature animals. Immunohistochemical localization showed that enalaprilat treatment caused an age-related recruitment of renin-containing juxtaglomerular cells. Conversely, ANG II pretreatment decreased basal and stimulated PR and AR secretion from immature fetal kidneys, but only inhibited PR secretion from mature kidneys. It also caused an age-related decrease in the percentage of renin-containing juxtaglomerular cells. These results suggest that ANG II feedback modulates not only the synthesis and content of renin, but the sensitivity of the coupling between stimulus and secretion. A critical observation of our study is that the higher renal tissue concentrations of prorenin and active renin in late gestation may be a consequence of reduced sensitivity to ANG II feedback; this is consistent with the increased plasma concentrations of renin found in near-term mammals.

Do osmotic forces play a role in renin secretion?

1988 ◽  
Vol 255 (1) ◽  
pp. F1-F10 ◽  
Author(s):  
O. Skott
Keyword(s):  
Secretory Granules ◽  
Proton Gradient ◽  
Renin Secretion ◽  
Renin Release ◽  
Juxtaglomerular Cells ◽  
Proton Gradients ◽  
Low Calcium ◽  
Release In Vitro

Secretory granules swell during exocytosis. Swelling may follow fusion and assist in extrusion of the granular content, or swelling may cause granular fusion with the plasmalemma. A granular proton gradient has been suggested to be involved in such preexocytic granular swelling. Exocytosis of renin from juxtaglomerular cells of isolated preparations is very sensitive to changes in the extracellular osmolality. Extracellular hyposmolality causes swelling of secretory granules, fusions between peripherally located granules and plasmalemma, and an increased number of release episodes. Induction of granule swelling at constant extracellular osmolality also stimulates renin release. Newly recruited renin granules are osmosensitive, and a high extracellular osmolality blocks secretion induced by other means (low calcium). Dissipation of granular proton gradients inhibits renin release without affecting the osmosensitivity. Thus, in renin release in vitro, a granular swelling precedes fusion and exocytosis, and a granular proton gradient may contribute to preexocytic swelling when extracellular osmolality is constant. The osmosensitivity may be important for macula densamediated renin release.

scholarly journals Analysis of the calcium paradox of renin secretion

2018 ◽  
Vol 315 (4) ◽  
pp. F834-F843 ◽  
Author(s):  
D. Steppan ◽  
L. Pan ◽  
K. W. Gross ◽  
A. Kurtz
Keyword(s):  
Light Chain ◽  
Myosin Light Chain ◽  
Calcium Concentration ◽  
Inhibitory Effect ◽  
Extracellular Calcium ◽  
Renin Secretion ◽  
Calcium Handling ◽  
Juxtaglomerular Cells ◽  
Extracellular Calcium Concentration ◽  
Electron Microscopical

The secretion of the protease renin from renal juxtaglomerular cells is enhanced by subnormal extracellular calcium concentrations. The mechanisms underlying this atypical effect of calcium have not yet been unraveled. We therefore aimed to characterize the effect of extracellular calcium concentration on calcium handling of juxtaglomerular cells and on renin secretion in more detail. For this purpose, we used a combination of experiments with isolated perfused mouse kidneys and direct calcium measurements in renin-secreting cells in situ. We found that lowering of the extracellular calcium concentration led to a sustained elevation of renin secretion. Electron-microscopical analysis of renin-secreting cells exposed to subnormal extracellular calcium concentrations revealed big omega-shaped structures resulting from the intracellular fusion and subsequent emptying of renin storage vesicles. The calcium concentration dependencies as well as the kinetics of changes were rather similar for renin secretion and for renovascular resistance. Since vascular resistance is fundamentally influenced by myosin light chain kinase (MLCK), myosin light chain phosphatase (MLCP), and Rho-associated protein kinase (Rho-K) activities, we examined the effects of MLCK-, MLCP-, and Rho-K inhibitors on renin secretion. Only MLCK inhibition stimulated renin secretion. Conversely, inhibition of MCLP activity lowered perfusate flow and strongly inhibited renin secretion, which could not be reversed by lowering of the extracellular calcium concentration. Renin-secreting cells and smooth muscle cells of afferent arterioles showed immunoreactivity of MLCK. These findings suggest that the inhibitory effect of calcium on renin secretion could be explained by phosphorylation-dependent processes under control of the MLCK.

Calcium in the control of renin release

1978 ◽  
Vol 235 (1) ◽  
pp. F22-F25 ◽  
Author(s):  
C. S. Park ◽  
R. L. Malvin
Keyword(s):  
Incubation Medium ◽  
Inhibitory Action ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Renin Release ◽  
Juxtaglomerular Cells ◽  
High K ◽  
Intracellular Ca ◽  
K Concentration ◽  
Cortical Slices

The effect of Ca concentrations in the incubation medium and of estimated intracellular Ca concentrations on renin release was examined with use of pig renal cortical slices. In addition, the Ca requirement for the epinephrine stimulatory effect and for the ouabain inhibitory action on renin release was also tested. In mediums containing 5.9 mM K, variations in Ca concentration had no effect on renin release. In contrast, when the K concentration was 59 mM, a significant inhibition of renin release was attained with all concentrations of calcium. The inhibition of renin release in high K mediums by Ca was attributed to an increase in the intracellular Ca concentration. In addition, both the stimulatory effect of epinephrine and the inhibitory effect of ouabain on renin release required Ca in the medium. These results support the hypothesis that the control of renin secretion is mediated, in part, by changes in the intracellular concentration of Ca, most likely in the juxtaglomerular cells.

Guanosine 3',5'-cyclic monophosphate as a mediator of inhibition of renin release

1988 ◽  
Vol 255 (3) ◽  
pp. F474-F478 ◽  
Author(s):  
W. L. Henrich ◽  
E. A. McAllister ◽  
P. B. Smith ◽  
W. B. Campbell
Keyword(s):  
Methylene Blue ◽  
Arachidonic Acid ◽  
Inhibitory Effect ◽  
Renin Release ◽  
Juxtaglomerular Cells ◽  
Cyclic Monophosphate ◽  
Direct Inhibitory Effect ◽  
Cortical Slices

The role of guanosine 3',5'-cyclic monophosphate (cGMP) as an inhibitory mediator of tissue renin release was examined in two different in vitro preparations. In rat superficial cortical slices, renin release stimulated by isoproterenol (10(-5) M) was ablated by atriopeptin III (ANP, 2.1 x 10(-8) M), nitroprusside (NP, 10(-3) M), and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 10(-3) and 10(-6) M). Arachidonic acid (10(-3) M)-stimulated renin release was also inhibited by ANP and 8-BrcGMP (10(-3) and 10(-6) M). Both ANP and NP increased tissue cGMP concentrations significantly (P less than 0.05), but neither had an effect on adenosine 3',5'-cyclic monophosphate (cAMP) concentrations. When methylene blue (10(-5) M), an inhibitor of guanylate cyclase, was added to slices incubated with isoproterenol and ANP, the inhibition of renin release by ANP was abolished. These results were confirmed in a preparation of isolated cultured rat juxtaglomerular cells. In these cells, isoproterenol induced a significant increase (58%, P less than 0.01) in renin release, which was inhibited by the addition of 8-BrcGMP (10(-6) M). These data demonstrate a direct inhibitory effect of ANP on isoproterenol- and arachidonic acid-induced renin release. The results with NP, 8-BrcGMP, and methylene blue suggest that cGMP is an intracellular mediator of this inhibition.

Sign in / Sign up

Export Citation Format

Share Document