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World J Nephrol. May 6, 2015; 4(2): 307-312
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.307
Species differences in regulation of renal proximal tubule transport by certain molecules
George Seki, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Shoko Horita
George Seki, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Shoko Horita, Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-0033, Japan
Author contributions: All the authors contributed to writing of this manuscript.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: George Seki, MD, Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. georgeseki-tky@umin.ac.jp
Telephone: +81-3-38155411 Fax: +81-3-58008806
Received: November 26, 2014
Peer-review started: November 27, 2014
First decision: December 18, 2014
Revised: December 24, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: May 6, 2015
Processing time: 163 Days and 20.8 Hours
Abstract

Renal proximal tubules (PTs) play important roles in the regulation of acid/base, plasma volume and blood pressure. Recent studies suggest that there are substantial species differences in the regulation of PT transport. For example, thiazolidinediones (TZDs) are widely used for the treatment of type 2 diabetes mellitus, but the use of TZDs is associated with fluid overload. In addition to the transcriptional enhancement of sodium transport in distal nephrons, TZDs rapidly stimulate PT sodium transport via a non-genomic mechanism depending on peroxisome proliferator activated receptor γ/Src/epidermal growth factor receptor (EGFR)/MEK/ERK. In mouse PTs, however, TZDs fail to stimulate PT transport probably due to constitutive activation of Src/EGFR/ERK pathway. This unique activation of Src/ERK may also affect the effect of high concentrations of insulin on mouse PT transport. On the other hand, the effect of angiotensin II (Ang II) on PT transport is known to be biphasic in rabbits, rats, and mice. However, Ang II induces a concentration-dependent, monophasic transport stimulation in human PTs. The contrasting responses to nitric oxide/guanosine 3’,5’-cyclic monophosphate pathway may largely explain these different effects of Ang II on PT transport. In this review, we focus on the recent findings on the species differences in the regulation of PT transport, which may help understand the species-specific mechanisms underlying edema formation and/or hypertension occurrence.

Keywords: Renal proximal tubule; Thiazolidinediones; Peroxisome proliferator activated receptor γ; Insulin; Angiotensin II; Nitric oxide

Core tip: Renal proximal tubule (PT) transport is essential for the regulation of plasma volume and blood pressure. Several species differences are found as to the stimulatory effects of thiazolidinediones, insulin, and angiotensin II on PT sodium transport. This review focuses on this topic, which may be relevant to species-specific mechanisms underlying edema formation and/or hypertension occurrence.