Abstract
Metabolically generated acid is the major physiological stimulus for increasing proximal tubule citrate reabsorption, which leads to a decrease in citrate excretion. The activity of the Na-citrate cotransporter, NaDC-1, is increased in vivo by acid ingestion and in vitro by an acidic pH medium. In opossum kidney cells the acid stimulatory effect and the ability of endothelin-1 (ET-1) to stimulate NaDC-1 activity are both blocked by the endothelin B (ETB) receptor antagonist, BQ788. Acid feeding had no effect on brush border membrane NaDC-1 activity in mice in which ETB receptor expression was knocked out, whereas a stimulatory effect was found in wild-type mice. Using ET A/ETB chimeric and ETB C-terminal tail truncated constructs, ET-1 stimulation of NaDC-1 required a receptor C-terminal tail from either ET A or ETB. The ET-1 effect was greatest when either the ETB transmembrane domain and C-terminal tail were present or the ETB C-terminal tail was linked to the ET A transmembrane domain. This effect was smaller when the ETB transmembrane domain was linked to the ET A C-terminal tail. Thus, the acid-activated pathway mediating stimulation of NaDC-1 activity requires a functional ETB receptor in vivo and in vitro, as does acid stimulation of NHE3 activity. Since increased NaDC-1 and NHE3 activities constitute part of the proximal tubule adaptation to an acid load, these studies indicate that there are similarities in the signaling pathway mediating these responses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 895-904 |
| Number of pages | 10 |
| Journal | Kidney International |
| Volume | 78 |
| Issue number | 9 |
| DOIs | |
| State | Published - Nov 2010 |
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Keywords
- cell and transport physiology
- cell signaling
- chronic metabolic acidosis
- citraturia
- renal proximal tubule cell
ASJC Scopus subject areas
- Nephrology
Cite this
Acid regulation of NaDC-1 requires a functional endothelin B receptor. / Liu, Liping; Zacchia, Miriam; Tian, Xuefei; Wan, Laxiang; Sakamoto, Aiji; Yanagisawa, Masashi; Alpern, Robert J.; Preisig, Patricia A.
In: Kidney International, Vol. 78, No. 9, 11.2010, p. 895-904.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acid regulation of NaDC-1 requires a functional endothelin B receptor
AU - Liu, Liping
AU - Zacchia, Miriam
AU - Tian, Xuefei
AU - Wan, Laxiang
AU - Sakamoto, Aiji
AU - Yanagisawa, Masashi
AU - Alpern, Robert J.
AU - Preisig, Patricia A.
PY - 2010/11
Y1 - 2010/11
N2 - Metabolically generated acid is the major physiological stimulus for increasing proximal tubule citrate reabsorption, which leads to a decrease in citrate excretion. The activity of the Na-citrate cotransporter, NaDC-1, is increased in vivo by acid ingestion and in vitro by an acidic pH medium. In opossum kidney cells the acid stimulatory effect and the ability of endothelin-1 (ET-1) to stimulate NaDC-1 activity are both blocked by the endothelin B (ETB) receptor antagonist, BQ788. Acid feeding had no effect on brush border membrane NaDC-1 activity in mice in which ETB receptor expression was knocked out, whereas a stimulatory effect was found in wild-type mice. Using ET A/ETB chimeric and ETB C-terminal tail truncated constructs, ET-1 stimulation of NaDC-1 required a receptor C-terminal tail from either ET A or ETB. The ET-1 effect was greatest when either the ETB transmembrane domain and C-terminal tail were present or the ETB C-terminal tail was linked to the ET A transmembrane domain. This effect was smaller when the ETB transmembrane domain was linked to the ET A C-terminal tail. Thus, the acid-activated pathway mediating stimulation of NaDC-1 activity requires a functional ETB receptor in vivo and in vitro, as does acid stimulation of NHE3 activity. Since increased NaDC-1 and NHE3 activities constitute part of the proximal tubule adaptation to an acid load, these studies indicate that there are similarities in the signaling pathway mediating these responses.
AB - Metabolically generated acid is the major physiological stimulus for increasing proximal tubule citrate reabsorption, which leads to a decrease in citrate excretion. The activity of the Na-citrate cotransporter, NaDC-1, is increased in vivo by acid ingestion and in vitro by an acidic pH medium. In opossum kidney cells the acid stimulatory effect and the ability of endothelin-1 (ET-1) to stimulate NaDC-1 activity are both blocked by the endothelin B (ETB) receptor antagonist, BQ788. Acid feeding had no effect on brush border membrane NaDC-1 activity in mice in which ETB receptor expression was knocked out, whereas a stimulatory effect was found in wild-type mice. Using ET A/ETB chimeric and ETB C-terminal tail truncated constructs, ET-1 stimulation of NaDC-1 required a receptor C-terminal tail from either ET A or ETB. The ET-1 effect was greatest when either the ETB transmembrane domain and C-terminal tail were present or the ETB C-terminal tail was linked to the ET A transmembrane domain. This effect was smaller when the ETB transmembrane domain was linked to the ET A C-terminal tail. Thus, the acid-activated pathway mediating stimulation of NaDC-1 activity requires a functional ETB receptor in vivo and in vitro, as does acid stimulation of NHE3 activity. Since increased NaDC-1 and NHE3 activities constitute part of the proximal tubule adaptation to an acid load, these studies indicate that there are similarities in the signaling pathway mediating these responses.
KW - cell and transport physiology
KW - cell signaling
KW - chronic metabolic acidosis
KW - citraturia
KW - renal proximal tubule cell
UR - http://www.scopus.com/inward/record.url?scp=77958110836&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958110836&partnerID=8YFLogxK
U2 - 10.1038/ki.2010.264
DO - 10.1038/ki.2010.264
M3 - Article
C2 - 20703215
AN - SCOPUS:77958110836
VL - 78
SP - 895
EP - 904
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 9
ER -