Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kidney collecting duct principal cells are the main source of stanniocalcin-1 (STC-1) production and secretion. From there, the hormone targets thick ascending limb and distal convoluted tubule cells, as well as collecting duct cells. More specifically, STC-1 targets their mitochondria to exert putative antiapoptotic effects. Two distal tubule cell lines serve as models of STC-1 production and/or mechanism of action. Madin-Darby canine kidney-1 (MDCK-1) cells mimic collecting duct cells in their synthesis of STC-1 ligand and receptor, whereas inner medullary collecting duct-3 (IMCD-3) cells respond to additions of STC-1 by increasing their respiration rate. In the present study, MDCK cell STC-1 secretion was examined under normal and hypertonic conditions, vectorally, and in response to hormones and signal transduction pathway activators/inhibitors. STC-1 receptor regulation was monitored in both cell lines in response to changing ligand concentration. The results showed that NaCl-induced hypertonicity had concentration-dependent stimulatory effects on STC-1 secretion, as did the PKC activator TPA. Calcium and ionomycin were inhibitory, whereas calcium receptor agonists had no effect. Angiotensin II, aldosterone, atrial natriuretic factor, antidiuretic hormone, and forskolin also had no effects. Moreover, STC-1 secretion exhibited no vectoral preference. STC-1 receptors were insensitive to homologous downregulation in both cell lines. In contrast, they were upregulated when STC-1 secretion was inhibited by calcium. The findings suggest that hypertonicity-induced STC-1 secretion is regulated through PKC activation and that high intracellular calcium levels are a potent inhibitor of release. More intriguingly, the results suggest that the receptor may not accompany STC-1 in its passage to the mitochondria.
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PMID:Stanniocalcin-1 secretion and receptor regulation in kidney cells. 1819 3

Renal stanniocalcin-1 (STC-1) is made by collecting duct principal cells for autocrine and paracrine targeting of the distal nephron. While the underlying purpose of this targeting is poorly understood, increased targeting is tied to changes in extracellular fluid (ECF) balance. For example, water deprivation is a potent stimulator of renal STC-1 gene activity in both rats and mice. The effects are most evident in cortical kidney where transcript levels are increased as much as 8-fold, as compared to 2-fold in the papilla. As is now known, this gene upregulation occurs in response to the dual consequences of water deprivation; hypertonicity followed by hypovolemia. The cortical gene has proven to be uniquely responsive to hypertonicity and that in papilla to hypovolemia; the implication being that STC-1 has different roles in the two zones, both of which are somehow related to ECF balance. The role of arginine vasopressin (AVP) in maintaining ECF balance is well established. Moreover, hypertonicity and hypovolemia are, respectively, the primary and secondary stimulators of AVP release. Therefore the present study explored the hypothesis that AVP was responsible for inducing the STC-1 gene in one or both zones. The results showed that this was indeed the case. AVP had time and dose-dependent stimulatory effects on the gene in both rat and mouse cortical kidney. In the papilla, however, gene regulation was more complex, as AVP was inhibitory in rats but stimulatory in mice. Further studies on papilla revealed that angiotensin II (ANG II) was stimulatory in rats, but inhibitory in mice. Moreover, ANG II attenuated the stimulatory effects of AVP in mouse cortex and papilla. Receptor agonist studies revealed that the effects of AVP in both zones were mediated exclusively through the V2 receptor (V1a, V1b and oxytocin-specific agonists had no effect). The findings serve to further implicate STC-1 in the renal control of ECF balance.
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PMID:Vasopressin controls stanniocalcin-1 gene expression in rat and mouse kidney. 2186 41