Regulation of collecting duct water permeability independent of cAMP-mediated AVP response

Abstract

We have used the isolated perfused tubule technique, measurements of adenosine 3',5'-cyclic monophosphate (cAMP) content in single tubules, and freeze-fracture electron microscopy to study the basis of high vasopressin-independent (basal) osmotic water permeability (Pf) in the terminal inner medullary collecting duct (IMCD) of the rat. The results confirmed the observation that the basal Pf of the terminal IMCD is considerably higher than that of the initial IMCD. They also showed that the basal Pf of the terminal IMCD is regulated by in vivo factors related to water intake, such that a very high vasopressin-independent Pf can be induced in isolated tubules by prior in vivo thirsting. Tubules from thirsted rats did not display elevated urea permeabilities, nor did they exhibit measurable cAMP levels in the absence of exogenous vasopressin, indicating that the high basal Pf was not due to residual binding of vasopressin to its receptors. Freeze-fracture studies in thirsted rats demonstrated the presence of intramembrane particle (IMP) clusters in both initial and terminal IMCD, with more in the latter. Water loading of the rats suppressed the incidence of clusters almost entirely but did not fully suppress the basal Pf in the terminal IMCD, raising the possibility that a component of transepithelial water transport may occur independently of the vasopressin-regulated IMP clusters. On the basis of these results, we conclude that the vasopressin-independent Pf in the terminal IMCD can be stably elevated to very high levels in response to in vivo thirsting. This elevation appears to be due to a chronic conditioning effect mediated by unknown in vivo factors and is not due to the short-term cAMP-mediated regulatory effect of vasopressin.

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.

“…After 35 d of treatment with lithium, rats were returned to a normal diet, without lithium, for 7 d. This resulted in an increase of about fourfold in urine osmolality, which was paralleled by a similar increase in AQP2 expression (Table I). Consistent with the known large variation in urine osmolality in normal rats (20), the urine osmolalities measured after cessation of lithium treatment were not significantly different from the controls. However, the mean value was only two thirds of that seen in the controls.…”

Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet.

“…We, like others, found that rats fed a normal (18%) protein diet have basal and AVP-stimulated P f values which are higher in terminal IMCDs than in initial IMCDs (14,33,34). Feeding rats 8% protein did not change basal P f values in either IMCD subsegment, but the 8% protein diet led to significantly lower AVP-stimulated P f values in terminal IMCDs, but not in initial IMCDs.…”

Rat renal arcade segment expresses vasopressin-regulated water channel and vasopressin V2 receptor.

“…Maximal concentrating capacity in response to acute administration of vasopressin is markedly enhanced when the experimental subject is pre-conditioned by restriction of water intake (31,32). We have demonstrated that this conditioning phenomenon is due in part to long-term upregulation of water permeability in the collecting duct (33), which in turn is due to a marked elevation in the level of AQP2 expression in the medullary collecting duct (15). The increase in AQP2 expression is thought to be due to a direct action of vasopressin on collecting duct cells (15), most likely by cAMP-mediated transcriptional activation (34,35).…”