Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation.

Objective and design: The aim of this study is to evaluate the expression of the histamine receptors, particularly focusing on the HR 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 (HR antagonist), ranitidine 10 µM (HR antagonist), GSK189254 1 µM (HR antagonist) or JNJ7777120 10 µM (HR 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 IP production, shifted to the right by chlorpheniramine maleate, and elicited a double bell-shaped curve for cAMP production, partially suppressed by the selective HR, HR and HR 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. [ABSTRACT FROM AUTHOR]