Histamine type 1-receptor activation by low dose of histamine undermines human glomerular slit diaphragm integrity

Veglia, Eleonora; Pini, Alessandro; Moggio, Aldo; Grange, Cristina; Premoselli, Federica; Miglio, Gianluca; Tiligada, Ekaterini; Fantozzi, Roberto; Chazot, Paul L.; Rosa, Arianna Carolina

doi:10.1016/j.phrs.2016.10.011

Cited by 12 publications

(30 citation statements)

References 58 publications

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“…Indeed, as reported in Supplementary Fig. 1 and consistent with previous data in the literature [9][10][11], HDC enzyme is expressed by residential cells both within the glomerulus and the tubules.…”

Section: Effect Of Jnj39758979 On Tubular Reabsorption Processessupporting

confidence: 92%

“…Histamine is a pleiotropic amine, historically implicated in several immune-inflammatory processes. It acts through four subtypes of G-protein coupled receptors, named histamine H1-4 receptors (H1-4Rs), which are differentially expressed in various organs, including the kidney included [6][7][8][9]. Histamine synthesis is catalysed by the rate-limiting enzyme histidine decarboxylase (HDC), mainly expressed in the "professional" mast cell.…”

Section: Introductionmentioning

confidence: 99%

“…Histamine synthesis is catalysed by the rate-limiting enzyme histidine decarboxylase (HDC), mainly expressed in the "professional" mast cell. However, HDC has been also found in the proximal tubule and human podocytes [9][10][11]. Actually, the first evidence for a possible role of histamine in diabetic nephropathy was provided in the 1960s when, concurrent with an increased tissue HDC activity, an increased level of this amine was observed in the kidney of diabetic animals [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Histamine H 4 receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice

Pini

Grange

Veglia

et al. 2018

Pharmacological Research

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Due to the incidence of diabetes and the related morbidity of diabetic nephropathy, identification of new therapeutic strategies represents a priority. In the last few decades new and growing evidence on the possible role of histamine in diabetes has been provided. In particular, the histamine receptor HR is emerging as a new promising pharmacological target for diabetic nephropathy. The aim of this study was to evaluate the efficacy of selective HR antagonism by JNJ39758979 on the prevention of diabetic nephropathy progression in a murine model of diabetes induced by streptozotocin injection. JNJ39758979 (25, 50, 100 mg/kg/day p.o.) was administered for 15 weeks starting from the onset of diabetes. Functional parameters were monitored throughout the experimental period. JNJ39758979 did not significantly affect glycaemic status or body weight. The urine analysis indicated a dose-dependent inhibitory effect of JNJ39758979 on Albumin-Creatinine-Ratio, the Creatinine Clearance, the 24 h urine volume, and pH urine acidification (P < 0.05). The beneficial effects of JNJ39758979 on renal function paralleled comparable effects on renal morphological integrity. These effects were sustained by a significant immune infiltration and fibrosis reduction. Notably, megalin and sodium-hydrogen-exchanger 3 expression levels were preserved. Our data suggest that the HR participates in diabetic nephropathy progression through both a direct effect on tubular reabsorption and an indirect action on renal tissue architecture via inflammatory cell recruitment. Therefore, HR antagonism emerges as a possible new multi-mechanism therapeutic approach to counteract development of diabetic nephropathy development.

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Section: Effect Of Jnj39758979 On Tubular Reabsorption Processessupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Histamine H 4 receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice

Pini

Grange

Veglia

et al. 2018

Pharmacological Research

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“…The H 1 receptors were correlated with a decrease in the ultrafiltration coefficient induced by histamine (Ichikawa & Brenner, ). These data are consistent with the localisation of H 1 receptor on podocytes (Veglia et al, ). Interestingly, histamine affects the disruption of cell‐to‐cell contact, via H 1 receptor activation, in an in vitro model of human immortalised podocytes.…”

Section: The Role Of Histamine In the Kidneyssupporting

confidence: 92%

“…The confocal analysis revealed that in human podocytes, only H 1 receptors were localised on the cell membrane. H 1 receptor expression was confirmed by the saturation binding analysis (Veglia et al, ). Moreover, histamine challenge evoked a sigmoidal dose‐dependent increase in IP 3 , the second messenger involved in the H 1 receptor signalling pathway, but not in cAMP, downstream signal of the histamine receptors (Veglia et al, ).…”

Section: The Histaminergic Machinery In the Kidneysmentioning

confidence: 95%

Histamine in the kidneys: what is its role in renal pathophysiology?

Grange

Gurrieri

Verta

et al. 2019

British J Pharmacology

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Starting with a role for histamine role in renal haemodynamics, evidence has accumulated, over time, suggesting a wider range of actions on renal function and this has renewed interest in the pathophysiological role of histamine in the kidney. Here we provide an up-to-date review of this topic. As the kidney expresses enzymes that synthesize and metabolise histamine, along with its receptors, all the components for histaminergic transmission are present in this tissue. The distribution of histamine receptors matches a wide range of effects. We address the questions of the redundancy of H 1 and H 2 receptors in renal haemodynamics, the complementary role of H 1 and H 4 receptors in renal filtration and reabsorption, and the dichotomy between local and neuronal H 1 and H 3 receptors. Experimental models of renal disease raise the possibility of new therapeutic approaches based on histamine. The effects of histamine on renal function are not yet fully understood and their elucidation is still ongoing. LINKED ARTICLES: This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit

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Histamine H4 receptor agonists induce epithelial-mesenchymal transition events and enhance mammosphere formation via Src and TGF-β signaling in breast cancer cells

Galarza

Delgado

Mohamad

et al. 2020

Biochemical Pharmacology

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Histamine type 1-receptor activation by low dose of histamine undermines human glomerular slit diaphragm integrity

Cited by 12 publications

References 58 publications

Histamine H 4 receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice

Histamine H 4 receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice

Histamine in the kidneys: what is its role in renal pathophysiology?

Histamine H4 receptor agonists induce epithelial-mesenchymal transition events and enhance mammosphere formation via Src and TGF-β signaling in breast cancer cells

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