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Target Concepts:
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Query: UNIPROT:P41181 (
collecting duct
)
5,183
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Insulin and
IGF-1
are recognized as powerful regulators of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. As previously described, these hormones both acutely increase ENaC activity in freshly isolated split open tubules and cultured principal cortical
collecting duct
cells. The present study was aimed at differentiating the effects of insulin and
IGF-1
on Na+ transport in immortalized mpkCCDcl4 cells and defining their interrelations. We have shown that both insulin and
IGF-1
applied basolaterally, but not apically, enhanced transepithelial Na+ transport in the mpkCCDcl4 cell line with EC50 values of 8.8 and 14.5 nM, respectively. Insulin treatment evoked phosphorylation of both insulin and
IGF-1
receptors, whereas the effects of
IGF-1
were more profound on its own receptor rather than the insulin receptor. AG-1024 and PPP, inhibitors of
IGF-1
and insulin receptor tyrosine kinase activity, diminished insulin- and
IGF-1
-stimulated Na+ transport in mpkCCDcl4 cells. The effects of insulin and
IGF-1
on ENaC-mediated currents were found to be additive, with insulin likely stimulating both
IGF-1
and insulin receptors. We hypothesize that insulin activates
IGF-1
receptors in addition to its own receptors, making the effects of these hormones interconnected.
...
PMID:Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells: implication for ENaC-mediated Na+ reabsorption. 2565 58
Since its identification as the underlying molecular cause of Bartter's syndrome type 3, ClC-Kb (ClC-K2 in rodents, henceforth it will be referred as ClC-Kb/2) is proposed to play an important role in systemic electrolyte balance and blood pressure regulation by controlling basolateral Cl(-) exit in the distal renal tubular segments from the cortical thick ascending limb to the outer medullary
collecting duct
. Considerable experimental and clinical effort has been devoted to the identification and characterization of disease-causing mutations as well as control of the channel by its cofactor, barttin. However, we have only begun to unravel the role of ClC-Kb/2 in different tubular segments and to reveal the regulators of its expression and function, e.g., insulin and
IGF-1
. In this review we discuss recent experimental evidence in this regard and highlight unexplored questions critical to understanding ClC-Kb/2 physiology in the kidney.
...
PMID:New perspective of ClC-Kb/2 Cl- channel physiology in the distal renal tubule. 2679 67
