Role of the Rhesus glycoprotein, Rh B glycoprotein, in renal ammonia excretion

Abstract

Rh B glycoprotein (Rhbg) is a member of the Rh glycoprotein family of ammonia transporters. In the current study, we examine Rhbg's role in basal and acidosis-stimulated acid-base homeostasis. Metabolic acidosis induced by HCl administration increased Rhbg expression in both the cortex and outer medulla. To test the functional significance of increased Rhbg expression, we used a Cre-loxP approach to generate mice with intercalated cell-specific Rhbg knockout (IC-Rhbg-KO). On normal diet, intercalated cell-specific Rhbg deletion did not alter urine ammonia excretion, pH, or titratable acid excretion significantly, but it did decrease glutamine synthetase expression in the outer medulla significantly. After metabolic acidosis was induced, urinary ammonia excretion was significantly less in IC-Rhbg-KO than in control (C) mice on days 2-4 of acid loading, but not on day 5. Urine pH and titratable acid excretion and dietary acid intake did not differ significantly between acid-loaded IC-Rhcg-KO and C mice. In IC-Rhbg-KO mice, acid loading increased connecting segment (CNT) cell and outer medullary collecting duct principal cell Rhbg expression. In both C and IC-Rhbg-KO mice, acid loading decreased glutamine synthetase in both the cortex and outer medulla; the decrease on day 3 was similar in IC-Rhbg-KO and C mice, but on day 5 it was significantly greater in IC-Rhbg-KO than in C mice. We conclude 1) intercalated cell Rhbg contributes to acidosis-stimulated renal ammonia excretion, 2) Rhbg in CNT and principal cells may contribute to renal ammonia excretion, and 3) decreased glutamine synthetase expression may enable normal rates of ammonia excretion under both basal conditions and on day 5 of acid loading in IC-Rhbg-KO mice.

Branchial NH4+-dependent acid–base transport mechanisms and energy metabolism of squid (Sepioteuthis lessoniana) affected by seawater acidification

“…The present work further demonstrates that gene transcripts coding for Na + /H + exchanger 3 (NHE3) and Rh protein (RhP), which are essential for proton equivalent transport in vertebrates [27,28,44,45] are also expressed in the cephalopod gill. NKA-rich cells (NaRs) located in the ion-transporting inner epithelium of the 3 order lamellae of the cephalopod gill showed positive immunoreactivity for VHA (basolateral), NHE3 (apical) and RhP (apical) using antibodies specifically designed for this species.…”

“…This net export of proton equivalents further suggests that NH 4 + excretion represents an important mechanism that contributes to acid-base balance in cephalopods. Interestingly, the cephalopod gill shows many morphological and functional similarities to the collecting duct of the mammalian kidney, where NH 4 + is transported to the luminal space via Rh glycoproteins and V-type H + -ATPase [45]. In the cephalopod gill, the semi-tubular structure of the 3°gill lamellae creates a luminal space into which NH 4 + is secreted by the interplay of RhP and NHE3 (Figure 9).…”

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

“…Collecting duct ammonia secretion involves parallel H 1 and NH 3 secretion (59). NH 3 secretion appears to involve transport by the Rhesus glycoproteins Rhbg and Rhcg, ammonia-specific transporters expressed in the collecting duct (60)(61)(62). Basolateral Na 1 -K 1 -ATPase contributes to IMCD ammonia secretion through its ability to transport NH 4 1 (63).…”

Ammonia excretion in mytilid mussels is facilitated by ciliary beating

“…TAM excretion requires controlled interaction of basolateral uptake and apical release of TAM. In vertebrates, this process is potentially differentially mediated by Rhbg and Rhcg located in basolateral and apical membranes, respectively (Bishop et al, 2010;Weiner and Verlander, 2010), but in invertebrates such as crustaceans and bivalves, so far only one primitive Rh protein has been described (Martin et al, 2011;Zhang et al, 2012). Consequently, an alternative model of vesicular TAM trapping has been suggested for crustaceans involving VHA and the Rh protein located in the membranes of intracellular vesicles (Weihrauch et al, 2002).…”