Vasopressin controls stanniocalcin-1 gene expression in rat and mouse kidney

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.

► Vasopressin has time and dose-dependent stimulatory effects in rat and mouse cortical kidney.
► Vasopressin is inhibitory in rat medulla but stimulatory in mouse medulla.
► In both zones, vasopressin operates exclusively though the V2 receptor (not V1a, V1b or oxytocin receptors).
► Angiotensin II attenuates the stimulatory effects of vasopressin in mouse kidney.
► Collectively the data argues strongly for a role of renal STC-1 in the maintenance of ECF balance.