Inhibitory effect of Ca2+ on renin secretion elicited by chemiosmotic stimuli through actomyosin mediation

Chun Sik Park, Hyun Sang Lee, Sunghoe Chang, Thomas W. Honeyman, Changgi D. Hong

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Abstract

We had previously shown that several experimental manipulations, which are likely to produce osmotic swelling of renin secretory granules, stimulate secretion of renin (C. S. Park, T. W. Honeyman, S. K. Ha, H. K. Choi, C. L. Chung, and C. D. Hong. J. Pharmacol. Exp. Ther. 259: 211-218, 1991). In subsequent studies, Ca2+ was found to block the stimulation of renin secretion evoked by osmotic swelling of renin secretion granules [Park, Hong, and Honeyman, Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F793-F798, 1992]. Furthermore, evidence from our recent studies indicates that myosin light chain kinase (MLCK) might be involved in the inhibition of renin secretion through Ca2+ -calmodulin. In the present study we investigate the possibility that MLCK might mediate the inhibitory action of Ca2+ on renin secretion stimulated by osmotic swelling of renin secretory granules. Rat renal cortical slices were incubated under a variety of experimental conditions that would produce osmotic swelling of renin secretory granules. Incubation in hypotonic KCl medium, isosmotic NH4Cl or CH3COONH4 medium, or isosmotic KCl or CH3COOK medium plus nigericin in the absence of Ca2+ all produced a significant increase in renin secretion 2- to 14-fold (P < 0.001). Ca2+ added to all of these media partially or completely blocked the stimulatory effects (P < 0.001). This inhibitory effect of Ca2+ was significantly blocked by ML-9 (10 4 M, P < 0.001), a putative specific inhibitor of the Ca2+-calmodulin-dependent MLCK. Taken together, the present findings support the idea that the renin secretory response may involve chemiosmotic swelling of renin secretory granules. This pivotal step may be regulated by contractile actomyosin interaction, which is in turn modulated through the Ca2+ calmodulin-dependent activity of MLCK.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume271
Issue number1 40-1
StatePublished - 1 Jul 1996

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Actomyosin
Renin
Myosin-Light-Chain Kinase
Secretory Vesicles
Calmodulin
Nigericin
Kidney
Electrolytes

Keywords

  • exocytosis
  • hydrogen- adenosinetriphosphatase
  • myosin light chain
  • myosin light chain kinase
  • potassium/hydrogen exchange
  • renin secretory granule
  • stimulus-secretion coupling

Cite this

@article{c3f335e542d2414d81422c3e7bb4b55b,
title = "Inhibitory effect of Ca2+ on renin secretion elicited by chemiosmotic stimuli through actomyosin mediation",
abstract = "We had previously shown that several experimental manipulations, which are likely to produce osmotic swelling of renin secretory granules, stimulate secretion of renin (C. S. Park, T. W. Honeyman, S. K. Ha, H. K. Choi, C. L. Chung, and C. D. Hong. J. Pharmacol. Exp. Ther. 259: 211-218, 1991). In subsequent studies, Ca2+ was found to block the stimulation of renin secretion evoked by osmotic swelling of renin secretion granules [Park, Hong, and Honeyman, Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F793-F798, 1992]. Furthermore, evidence from our recent studies indicates that myosin light chain kinase (MLCK) might be involved in the inhibition of renin secretion through Ca2+ -calmodulin. In the present study we investigate the possibility that MLCK might mediate the inhibitory action of Ca2+ on renin secretion stimulated by osmotic swelling of renin secretory granules. Rat renal cortical slices were incubated under a variety of experimental conditions that would produce osmotic swelling of renin secretory granules. Incubation in hypotonic KCl medium, isosmotic NH4Cl or CH3COONH4 medium, or isosmotic KCl or CH3COOK medium plus nigericin in the absence of Ca2+ all produced a significant increase in renin secretion 2- to 14-fold (P < 0.001). Ca2+ added to all of these media partially or completely blocked the stimulatory effects (P < 0.001). This inhibitory effect of Ca2+ was significantly blocked by ML-9 (10 4 M, P < 0.001), a putative specific inhibitor of the Ca2+-calmodulin-dependent MLCK. Taken together, the present findings support the idea that the renin secretory response may involve chemiosmotic swelling of renin secretory granules. This pivotal step may be regulated by contractile actomyosin interaction, which is in turn modulated through the Ca2+ calmodulin-dependent activity of MLCK.",
keywords = "exocytosis, hydrogen- adenosinetriphosphatase, myosin light chain, myosin light chain kinase, potassium/hydrogen exchange, renin secretory granule, stimulus-secretion coupling",
author = "Park, {Chun Sik} and Lee, {Hyun Sang} and Sunghoe Chang and Honeyman, {Thomas W.} and Hong, {Changgi D.}",
year = "1996",
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language = "English",
volume = "271",
journal = "American Journal of Physiology - Cell Physiology",
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Inhibitory effect of Ca2+ on renin secretion elicited by chemiosmotic stimuli through actomyosin mediation. / Park, Chun Sik; Lee, Hyun Sang; Chang, Sunghoe; Honeyman, Thomas W.; Hong, Changgi D.

In: American Journal of Physiology - Cell Physiology, Vol. 271, No. 1 40-1, 01.07.1996.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Inhibitory effect of Ca2+ on renin secretion elicited by chemiosmotic stimuli through actomyosin mediation

AU - Park, Chun Sik

AU - Lee, Hyun Sang

AU - Chang, Sunghoe

AU - Honeyman, Thomas W.

AU - Hong, Changgi D.

PY - 1996/7/1

Y1 - 1996/7/1

N2 - We had previously shown that several experimental manipulations, which are likely to produce osmotic swelling of renin secretory granules, stimulate secretion of renin (C. S. Park, T. W. Honeyman, S. K. Ha, H. K. Choi, C. L. Chung, and C. D. Hong. J. Pharmacol. Exp. Ther. 259: 211-218, 1991). In subsequent studies, Ca2+ was found to block the stimulation of renin secretion evoked by osmotic swelling of renin secretion granules [Park, Hong, and Honeyman, Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F793-F798, 1992]. Furthermore, evidence from our recent studies indicates that myosin light chain kinase (MLCK) might be involved in the inhibition of renin secretion through Ca2+ -calmodulin. In the present study we investigate the possibility that MLCK might mediate the inhibitory action of Ca2+ on renin secretion stimulated by osmotic swelling of renin secretory granules. Rat renal cortical slices were incubated under a variety of experimental conditions that would produce osmotic swelling of renin secretory granules. Incubation in hypotonic KCl medium, isosmotic NH4Cl or CH3COONH4 medium, or isosmotic KCl or CH3COOK medium plus nigericin in the absence of Ca2+ all produced a significant increase in renin secretion 2- to 14-fold (P < 0.001). Ca2+ added to all of these media partially or completely blocked the stimulatory effects (P < 0.001). This inhibitory effect of Ca2+ was significantly blocked by ML-9 (10 4 M, P < 0.001), a putative specific inhibitor of the Ca2+-calmodulin-dependent MLCK. Taken together, the present findings support the idea that the renin secretory response may involve chemiosmotic swelling of renin secretory granules. This pivotal step may be regulated by contractile actomyosin interaction, which is in turn modulated through the Ca2+ calmodulin-dependent activity of MLCK.

AB - We had previously shown that several experimental manipulations, which are likely to produce osmotic swelling of renin secretory granules, stimulate secretion of renin (C. S. Park, T. W. Honeyman, S. K. Ha, H. K. Choi, C. L. Chung, and C. D. Hong. J. Pharmacol. Exp. Ther. 259: 211-218, 1991). In subsequent studies, Ca2+ was found to block the stimulation of renin secretion evoked by osmotic swelling of renin secretion granules [Park, Hong, and Honeyman, Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F793-F798, 1992]. Furthermore, evidence from our recent studies indicates that myosin light chain kinase (MLCK) might be involved in the inhibition of renin secretion through Ca2+ -calmodulin. In the present study we investigate the possibility that MLCK might mediate the inhibitory action of Ca2+ on renin secretion stimulated by osmotic swelling of renin secretory granules. Rat renal cortical slices were incubated under a variety of experimental conditions that would produce osmotic swelling of renin secretory granules. Incubation in hypotonic KCl medium, isosmotic NH4Cl or CH3COONH4 medium, or isosmotic KCl or CH3COOK medium plus nigericin in the absence of Ca2+ all produced a significant increase in renin secretion 2- to 14-fold (P < 0.001). Ca2+ added to all of these media partially or completely blocked the stimulatory effects (P < 0.001). This inhibitory effect of Ca2+ was significantly blocked by ML-9 (10 4 M, P < 0.001), a putative specific inhibitor of the Ca2+-calmodulin-dependent MLCK. Taken together, the present findings support the idea that the renin secretory response may involve chemiosmotic swelling of renin secretory granules. This pivotal step may be regulated by contractile actomyosin interaction, which is in turn modulated through the Ca2+ calmodulin-dependent activity of MLCK.

KW - exocytosis

KW - hydrogen- adenosinetriphosphatase

KW - myosin light chain

KW - myosin light chain kinase

KW - potassium/hydrogen exchange

KW - renin secretory granule

KW - stimulus-secretion coupling

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M3 - Article

VL - 271

JO - American Journal of Physiology - Cell Physiology

JF - American Journal of Physiology - Cell Physiology

SN - 0363-6143

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