H3 receptor renal expression in normal and diabetic rats
Summary (2 min read)
Introduction
- Recently, their group demonstrated the presence of the histamine H4 receptor (H4R) in resident renal cells of the loop of Henlé and its profound upregulation in the kidney of diabetic rats[1].
- In renal transplant patients the urinary and blood levels of histamine are elevated.
- In the kidney of diabetic rats, histamine was increased compared with controls[2].
- Basically, histamine has been reported to regulate the renal microcirculation, to increase salt and water excretion[3-5], decrease the ultrafiltration coefficient by reducing the total filtration surface area[4], and increase renin release[6].
- The aim of this study was to extend their previous observation on H4R in healthy and diabetic rats evaluating in the same specimens the renal expression of H3R.
Materials and Methods
- Animals, protocols, diabetes induction, biochemical and histological parameters have been previously reported[1].
- Conventional immunohistochemical procedures were employed as described.
- Renal sections were incubated overnight with anti-H3R (349–358) (2 µg/ml)[7], followed by a three-layer streptavidin–biotin–peroxidase complex staining method.
- After counterstaining with DAPI, photomicrographs were obtained by Apotome systems at x40 objective.
- Values are expressed as mean ± SEM positive cell/collecting duct percentage of individual rats (ten images/zone each) from the different experimental groups.
Results
- The immunohistochemical analysis (Fig. 1A) revealed a clear H3R-like immunoreactivity in control rats, predominantly in the renal medulla and the papilla.
- In contrast, in the cortex the immunoreactivity was generally very low, and no signal was detected in the glomeruli.
- Notably, when diabetic and non-diabetic animals were compared, a significant increase in immunoreactivity, suggestive of H3R receptor upregulation, was observed (Fig 1B).
- The above data, indicating a higher H3R-like immunoreactivity in the apical membrane of epithelial tubular cells mosty located in medulla and papilla, suggested a collecting duct expression profile for the receptor.
- To confirm this result, immunoflorescence co-staining was performed with AQP2, expressed in the apical membrane by collecting duct cells in the kidney.
Discussion
- The authors demonstrate for the first time that the H3R is mainly expressed in the apical membrane by collecting duct cells of the rat, and that this protein is significantly upregulated in the kidneys of diabetic animals.
- The authors histochemical data add the collecting duct cells to the growing list of non-neuronal H3R-expressing cells already reported[7-9], thus providing further evidence for a role of H3R in mediating non-neuronal histamine effects.
- The collecting duct plays a pivotal role in kidney function and homeostasis by regulating ions and water transport.
- The ability to concentrate urine is impaired in conditions such as diabetes insipidus, Histamine, whose levels have been reported to be increased in the kidney of diabetic animals[2], has been shown to increase salt and water excretion[8-10].
- Whether this receptor has a compensatory or pathological implication and its role as a pharmacological target in diabetic nephropathy remains to be established.
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Citations
21 citations
Cites background from "H3 receptor renal expression in nor..."
...Notably, 312 among them, both the H3R and the H4R have been reported to be profoundly upregulated at the 313 tubular level in STZ treated rats, which also displayed parallel renal damage (mostly again at the 314 tubular level) [33, 146]....
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...Notably, the majority of these data were obtained 112 before the clear demonstration of H3R peripheral expression [16, 30-34]....
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...independent, but sometimes contradictory; despite this heterogeniety, when viewing the timeline of 322 interest for histamine involvement in this disease (Figure 1) it appears phasic with a clear upturn 323 and renewal in interest in the last couple of years, thanks to the very recent discovery of a direct 324 effect of histamine on glycaemia [13, 16, 17] as well as a profound up-regulation of both H3R and 325 H4R in the diabetic animal kidney [33, 146]....
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16 citations
Cites background from "H3 receptor renal expression in nor..."
...nterestingly, we demonstrated that renal H3R is predominantly ocalized on the collecting duct epithelium [7], a major regulator of ater reabsorption....
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...Moreover, its expression was up-regulated in he kidney of both diabetic rats [7] and DBA2/J mice (Supplemenary Fig....
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14 citations
Cites background or methods or result from "H3 receptor renal expression in nor..."
...More recently, the use of both primary and immortalised renal cell types from different mammals (Table 1) allowed to identify not only the H1 receptor and H2 receptor, but also the more recently discovered H3 receptor and H4 receptor, in the nephron and collecting ducts (Pini et al., 2015; Rosa et al., 2013; Veglia et al., 2015, 2016)....
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...However, the data obtained from rats and humans indicated that H3 receptors are present in the resident epithelial cells of the collecting duct and that they are co‐localised with the vasopressin water channel aquaporin (AQP)‐2 (Pini et al., 2015; Veglia et al., 2015)....
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...Histamine receptors topology within the mammalian kidney based on current knowledge (Pini et al., 2015; Rosa et al., 2013; Sedor & Abboud, 1984; Sedor & Abboud, 1985; Veglia et al., 2015, 2016)....
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...Again, the data were obtained by both immunodetection and gene expression in both ex vivo and in vitro studies (Pini et al., 2015; Veglia et al., 2015) and were confirmed in vitro on human renal cells (Veglia et al....
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...The H3 receptor has surprisingly been found on the principal cells of the collecting duct, both in humans (Veglia et al., 2015) and in rats (Pini et al., 2015)....
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12 citations
12 citations
Cites background from "H3 receptor renal expression in nor..."
...Among these histamine receptor subtypes, H1 and H2 are expressed in the hearts and kidneys, and H3 is expressed in the ending of sympathetic nerves in these tissues (32, 33)....
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References
22 citations
14 citations