Modulation of renal Na-Pi cotransport by hormones acting via genomic mechanism and by metabolic factors

Abstract

The renal Na-Pi cotransport is subject to multiple regulatory inputs, such as endocrine, paracrine and intracrine. Among lipophilic, long-acting hormones that act via genomic mechanism, thyroid hormones, calcitriol, all-trans-retinoic acid stimulate, whereas glucocorticoids and estradiol inhibit the rate of Na-Pi cotransport across the brush border membrane of proximal tubules in vivo and/or across apical membrane of renal epithelial cells in vitro. Some findings suggest that these hormones may also influence Na-Pi cotransporter by modification of membrane microenvironment. It should be considered that Na-Pi cotransport can be modulated by lipophilic hormones by non-genomic signaling mechanisms such as sphingomyelin-ceramide pathway, NAD-cyclic ADP-ribose-Ca2+i pathway or by Ca2+ influx. Recent studies outline a basis for the putative intracrine signaling mechanisms that utilize Ca(2+)-releasing nucleotides, cyclic ADP-ribose, and nicotinic acid adenosine dinucleotide phosphate (NAADP), as novel second messengers for regulation of Na-Pi cotransport in response to changes of intermediary metabolic processes: gluconeogenesis, pentose phosphate pathway, polyamines and metabolism of fatty acids.

Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1αOHase-deficient mice

“…In the kidney, the role of 1,25(OH) 2 D in P i reabsorption, and more specifically its effect on the abundance of NaP i -IIa cotransporter in proximal tubules, is less clear. Conflicting results have been reported indicating that a possible action of 1,25(OH) 2 D on the NaP i -IIa cotransporter is dose dependent and depends on alterations in the level of PTH (8,19). As demonstrated recently, a genomic effect of low-P i diet on the upregulation of NaP i -IIa seems unlikely, because in cortical as well as juxtamedullary proximal tubular S1 and S3 segments of adult mice, the abundance of NaP i -IIa mRNA was not altered by a low-P i diet (17).…”

“…Because low-P i diet induces an upregulation of NaP i -IIb mRNA (23; Radanovic T, Wagner CA, Murer H, and Biber J, unpublished data), it could be envisaged that the action of 1,25(OH) 2 D is via a genomic mechanism that involves the vitamin D receptor (VDR) (2). The role of 1,25(OH) 2 D in the renal handling of P i is less clear, notably also because of the complexity rooted in an interrelationship with the status of parathyroid hormone (PTH) (8).…”

Hepatectomy-Related Hypophosphatemia

“…Dousa previously demonstrated that NAD inhibits renal Na/Pi transport mainly in response to metabolic stimuli, and suggested that NAD acts indirectly by first being converted to cyclic ADP-ribose, a potent stimulator of intracellular Ca 2+ mobilization. 33 According to this hypothesis, the increase in the cellular NAD levels is an important factor for renal Na/Pi transport activity. 33 Although many studies have assessed the association between NAD and Na/ Pi transport activity, the data are controversial.…”

“…33 According to this hypothesis, the increase in the cellular NAD levels is an important factor for renal Na/Pi transport activity. 33 Although many studies have assessed the association between NAD and Na/ Pi transport activity, the data are controversial. 34,35 In this study, we showed that the reduction in NaPi-II transporters occurs earlier than the increase in the renal NAD concentration after PH.…”

Raquitismo e osteomalacia

“…Vários genes participam da homeostase do P. Sua reabsorção, na borda em escova do túbulo contornado proximal renal, é feita pelo cotransportador de Na e P (NPT2) (47,48), cujo gene codificador está localizado no cromossomo 5 (5q35). O NPT2 sofre ação inativadora da fosfatonina, um hormônio peptídeo, produzido provavelmente pelos hepatócitos, cuja estrutura molecular não está totalmente identificada (34)(35)(36).…”