Abstract
The natriuretic hormone CCK exhibits its gene transcripts in total kidney extracts. To test the possibility of CCK acting as an intrarenal mediator of sodium excretion, we examined mouse kidneys by 1) an in situ hybridization technique for CCK mRNA in animals fed a normal- or a high-sodium diet; 2) immuno-electron microscopy for the CCK peptide, 3) an in situ hybridization method and immunohistochemistry for the CCK-specific receptor CCKAR; 4) confocal image analysis of receptor-mediated Ca2+ responses in isolated renal tubules; and 5) metabolic cage experiments for the measurement of urinary sodium excretion in high-salt-fed mice either treated or untreated with the CCKAR antagonist lorglumide. Results showed the CCK gene to be expressed intensely in the inner medulla and moderately in the inner stripe of the outer medulla, with the expression in the latter being enhanced by high sodium intake. Immunoreactivity for the CCK peptide was localized to the rough endoplasmic reticulum of the medullary interstitial cells in corresponding renal regions, confirming it to be a secretory protein. Gene transcripts, protein products, and the functional activity for CCKAR were consistently localized to the late proximal tubule segments (S2 and S3) in the medullary rays, and the outer stripe of the outer medulla. Lorglumide significantly diminished natriuretic responses of mice to a dietary sodium load without altering the glomerular filtration rate. These findings suggest that the medullary interstitial cells respond to body fluid expansion by CCK release for feedback regulation of the late proximal tubular reabsorption.
| Original language | English |
|---|---|
| Pages (from-to) | F20-F29 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 313 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
| Externally published | Yes |
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Keywords
- Ca image analysis
- Medullary interstitial cells
- Proximal tubule
- Sodium excretion
- Transmission electron microscopy
ASJC Scopus subject areas
- Physiology
- Urology
Cite this
Intrarenal signaling mediated by CCK plays a role in salt intake-induced natriuresis. / Takahashi-Iwanaga, Hiromi; Kimura, Shunsuke; Konno, Kohtarou; Watanabe, Masahiko; Iwanaga, Toshihiko.
In: American Journal of Physiology - Renal Physiology, Vol. 313, No. 1, 01.01.2017, p. F20-F29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intrarenal signaling mediated by CCK plays a role in salt intake-induced natriuresis
AU - Takahashi-Iwanaga, Hiromi
AU - Kimura, Shunsuke
AU - Konno, Kohtarou
AU - Watanabe, Masahiko
AU - Iwanaga, Toshihiko
PY - 2017/1/1
Y1 - 2017/1/1
N2 - The natriuretic hormone CCK exhibits its gene transcripts in total kidney extracts. To test the possibility of CCK acting as an intrarenal mediator of sodium excretion, we examined mouse kidneys by 1) an in situ hybridization technique for CCK mRNA in animals fed a normal- or a high-sodium diet; 2) immuno-electron microscopy for the CCK peptide, 3) an in situ hybridization method and immunohistochemistry for the CCK-specific receptor CCKAR; 4) confocal image analysis of receptor-mediated Ca2+ responses in isolated renal tubules; and 5) metabolic cage experiments for the measurement of urinary sodium excretion in high-salt-fed mice either treated or untreated with the CCKAR antagonist lorglumide. Results showed the CCK gene to be expressed intensely in the inner medulla and moderately in the inner stripe of the outer medulla, with the expression in the latter being enhanced by high sodium intake. Immunoreactivity for the CCK peptide was localized to the rough endoplasmic reticulum of the medullary interstitial cells in corresponding renal regions, confirming it to be a secretory protein. Gene transcripts, protein products, and the functional activity for CCKAR were consistently localized to the late proximal tubule segments (S2 and S3) in the medullary rays, and the outer stripe of the outer medulla. Lorglumide significantly diminished natriuretic responses of mice to a dietary sodium load without altering the glomerular filtration rate. These findings suggest that the medullary interstitial cells respond to body fluid expansion by CCK release for feedback regulation of the late proximal tubular reabsorption.
AB - The natriuretic hormone CCK exhibits its gene transcripts in total kidney extracts. To test the possibility of CCK acting as an intrarenal mediator of sodium excretion, we examined mouse kidneys by 1) an in situ hybridization technique for CCK mRNA in animals fed a normal- or a high-sodium diet; 2) immuno-electron microscopy for the CCK peptide, 3) an in situ hybridization method and immunohistochemistry for the CCK-specific receptor CCKAR; 4) confocal image analysis of receptor-mediated Ca2+ responses in isolated renal tubules; and 5) metabolic cage experiments for the measurement of urinary sodium excretion in high-salt-fed mice either treated or untreated with the CCKAR antagonist lorglumide. Results showed the CCK gene to be expressed intensely in the inner medulla and moderately in the inner stripe of the outer medulla, with the expression in the latter being enhanced by high sodium intake. Immunoreactivity for the CCK peptide was localized to the rough endoplasmic reticulum of the medullary interstitial cells in corresponding renal regions, confirming it to be a secretory protein. Gene transcripts, protein products, and the functional activity for CCKAR were consistently localized to the late proximal tubule segments (S2 and S3) in the medullary rays, and the outer stripe of the outer medulla. Lorglumide significantly diminished natriuretic responses of mice to a dietary sodium load without altering the glomerular filtration rate. These findings suggest that the medullary interstitial cells respond to body fluid expansion by CCK release for feedback regulation of the late proximal tubular reabsorption.
KW - Ca image analysis
KW - Medullary interstitial cells
KW - Proximal tubule
KW - Sodium excretion
KW - Transmission electron microscopy
UR - http://www.scopus.com/inward/record.url?scp=85021925591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021925591&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00539.2016
DO - 10.1152/ajprenal.00539.2016
M3 - Article
C2 - 28298361
AN - SCOPUS:85021925591
VL - 313
SP - F20-F29
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 0363-6127
IS - 1
ER -