Genomic and nongenomic dose-dependent biphasic effect of aldosterone on Na⁺/H⁺exchanger in proximal S3 segment: role of cytosolic calcium

Abstract

Leite-Dellova DC, Oliveira-Souza M, Malnic G, Mello-Aires M. Genomic and nongenomic dose-dependent biphasic effect of aldosterone on Na

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

“…The results of this research also indicated that MR and probably GR participate in the genomic and nongenomic effects of ALDO on [Ca 2+ ]i and on the Na + /H + exchanger. These data are in agreement with previous findings using RT-PCR that indicated the presence of these receptors in proximal S3 segments [230].…”

“…Apical Na + channel activity is the limiting step in the transport process, and it is likely that ALDO ultimately acts to increase the open time of existing ion channels and/ or increase the total number of such channels [225]. However, other protein targets have also been identified, including i) a luminal NHE3 exchanger in the colon [226,227] and the proximal tubule [228] and a basolateral NHE1 in the proximal tubule [229,230], ii) an Na + /K + -ATPase in human kidney proximal tubule (HKC11) cells [231], iii) a luminal thiazide-sensitive Na + /Cl − cotransporter in the distal renal tubule that appears to mediate Na+ reabsorption in response to volume depletion [232], and iv) a renal proximal H + -ATPase [233].…”

“…Several sites in the kidney, particularly cultured kidney cells, have been shown to be sensitive to non-genomic ALDO action [266], including principal cells that were freshly isolated from rabbits [267], the human distal colon [268], in vivo renal proximal tubules (S2 segment) [228], isolated renal proximal tubules (S3 segment) [229,233], medullary thick ascending limbs [269] and renal collecting duct cells [270]. Its non-genomic actions include effects on signal transduction pathways and ion transporters, such as the epithelial Na + channel [267], the Na + /H + exchanger [228,229,271,272] and the vacuolar H + -ATPase [230,233,258,259,273].…”

“…Additionally, it has been shown that through both genomic and non-genomic mechanisms, ALDO stimulates Na + reabsorption, K + secretion [280], Na + /H + exchange [230] and H + -ATPase [233] in the kidney, and Na + /H + exchange in vascular smooth muscle cells [281].…”

“…In addition, it was also shown that an elevation in [Ca 2+ ]i has the following effects: i) it serves as a second messenger in the ALDO-mediated initiation of nongenomic Na + /H + exchanger activation [271], and ii) it is a prerequisite for the genomic action of ALDO, and strong evidence indicates that pregenomic hormonal responses can influence genomic processes [284]. Therefore, we performed a study to clarify the genomic and nongenomic effects of ALDO on the Na + /H + exchanger and the role of [Ca 2+ ]i in these processes [230]. The experiments were performed using isolated rat proximal straight tubules (S3 segments) and fluorescent probes to measure pH intracellular recovery rates (pHi)r after the acidification of the pHi was induced by a NH 4 Cl pulse.…”