14] cited a close relationship between NO and AQP2 and suggested that NO stimulates the membrane insertion of AQP2 in renal epithelial cells.
11] In this previous study by Spector and colleagues, the authors showed that dehydration in rats led to a significant upregulation of AQP2 and AQP3 expression, thus providing presumptive evidence that AQPs are involved in water and solute transport.
However, the AQP2 water channel has one more role to play.
Changes of rat kidney AQP2 and Na,K ATPase mRNA expression in lithium-induced nephrogenic diabetes insipidus.
31) However, further research has suggested that other AQPs are present in the PCT More dramatic forms of NDI have been seen in patients with deficiencies in AQP2 or the ADH-receptors.
29) AQP4 is expressed in the CD cells, and facilitates water's exit from the basolateral membranes after AQP2 has facilitated uptake into the cells.
For example, NDI can result from AQP2 gene mutations, malfunction of ADH receptors, changes in gene expression, or trafficking malfunctions (the process of folding and transporting of newly synthesized AQP to the cell membrane).
In the absence of ADH, these AQP2 channels reside in intracellular vesicles and do not facilitate water reabsorption.
Elevated cAMP levels lead to the phosphorylation of the pre-synthesized AQP2 channels, and signals for their insertion into the cell membrane.
While malfunctions have been identified in each of these steps, most NDI cases have involved ADH-receptor mutations or disruption of the intracellular transport, rather than mutations of AQP2.
Without elevated cAMP, AQP2 is not inserted into the membrane, and water reabsorption is minimized.
Marples found that a 25 day course of lithium caused a 95% reduction in AQP2 in rats and the lithium-treated rats developed extreme polyuria, (38) excreting urine volumes equal to their body weight each day.