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.