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Durham University

Department of Biosciences

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Publication details for Dr P Chazot

Veglia, E., Grange, C., Pini, A, Moggio, A., Lanzi, C., Camussi, G., Chazot, P.L. & Rosa, A.C. (2015). Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation. Inflammation Research 64(3-4): 261-270.

Author(s) from Durham

Abstract

Objective and design
The aim of this study is to evaluate the expression of the histamine receptors, particularly focusing on the H4R in human renal tubules.
Material
The ex vivo evaluation was carried on specimens from human renal cortex. Primary and immortalized tubular epithelial cells (TECs) and the HK-2 cell line were used as in vitro models.
Treatment
Cells were pretreated for 10 min with chlorpheniramine maleate 10 μM (H1R antagonist), ranitidine 10 µM (H2R antagonist), GSK189254 1 µM (H3R antagonist) or JNJ7777120 10 µM (H4R antagonist), and then exposed to histamine (3 pM–10 nM) for 30 min.
Methods
The ex vivo evaluation on specimens from human renal cortex was performed by immunohistochemistry. The expression of histamine receptors on primary and immortalized TECs and the HK-2 cell line was evaluated at both gene (RT-PCR) and protein (immunocytofluorescence) levels. The pharmacological analysis was performed by TR-FRET measurements of second messenger (IP3 and cAMP) production induced by histamine with or without the selective antagonists.
Results
Our data revealed the presence of all histamine receptors in human tubules; however, only TECs expressed all the receptors. Indeed, histamine elicited a sigmoid dose–response curve for IP3 production, shifted to the right by chlorpheniramine maleate, and elicited a double bell-shaped curve for cAMP production, partially suppressed by the selective H2R, H3R and H4R antagonists when each added alone, and completely ablated when combined together.
Conclusions
Herein, we report the identification of all four histamine receptors in human renal tubules.