Stanniocalcin-1 secretion and receptor regulation in kidney cells.
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.
Sazonova
Olga
O
Dept. of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Univ. of Western Ontario, London, Ontario, Canada N6A 5C1.
James
Kathi A
KA
McCudden
Christopher R
CR
Segal
Daniel
D
Talebian
Asghar
A
Wagner
Graham F
GF
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney; D011493:Protein Kinase C / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology
D006023:Glycoproteins; D011956:Receptors, Cell Surface; D012965:Sodium Chloride; C051795:teleocalcin; D011493:Protein Kinase C; D002122:Calcium Chloride