Laboratory Investigation

Kidney International (1984) 26, 144–152; doi:10.1038/ki.1984.148

Actions and metabolism of histamine in glomeruli and tubules of the human kidney

John R Sedor1 and Hanna E Abboud1

1Division of Nephrology, Department of Medicine, Veterans Administration Medical Center, Case Western Reserve University and University Hospitals, Cleveland, Ohio

Correspondence: Dr H E Abboud, Division of Nephrology, Department of Medicine, Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, Ohio 44106, USA

Received 17 August 1983; Revised 7 February 1984.

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Abstract

Actions and metabolism of histamine in glomeruli and tubules of the human kidney. The effects of histamine on cAMP and cGMP accumulation and the intrarenal metabolism of histamine were studied in glomeruli and cortical tubules of nine human kidneys. Histamine stimulated cAMP but not cGMP accumulation in glomeruli (Delta + 100% to + 265%) in a dose- (10-6 to 10-4 M range) and time-dependent manner. This effect of histamine was inhibited by the histamine H2 antagonist cimetidine but not the H1 antagonist diphenhydramine. Moreover, the H2 agonist dimparit but not the H, agonist 2-pyridylethylamine stimulated cAMP accumulation. Histamine had no effect on cAMP or cGMP accumulation in tubules. Because the content of histamine (sime2 times 10-6 M) in glomeruli was far above the circulating levels of plasma histamine in humans (<10-8 M), we explored whether histamine is formed in human renal tissue. Incubation of glomeruli with 1 mM of the histamine precursor L-histidine resulted in an increase in histamine levels (+ Delta6.08 plusminus 0.5 pmoles/mg protein, N = 7 kidneys) while a marked drop in histamine levels was observed in tubules (-Delta13.8 plusminus 2.4 pmoles/mg protein, N = 7 kidneys). The increase in histamine levels in glomeruli was abolished by the histidine decarboxylase inhibitor bromocresine. These results indicate that human glomeruli have histamine H2 receptors, which mediate enhanced cAMP accumulation, and that glomeruli are major sites of histamine production in the human kidney. Histamine acting via cAMP may influence glomerular function of the human kidney.

Effets et métabolisme de l'histamine dans les glomérules et les tubules de rein humain. Les effets de l'histamine sur l'accumulation de cAMP et de cGMP, et le métabolisme intra-rénal de l'histamine ont été étudiés dans les glomérules et les tubules corticaux de neuf reins humains. L'histamine stimulait l'accumulation de cAMP mais non celle de cGMP dans les glomérules (Delta + 100% à 265%) de façon dose- (de 10-6 à 10-4 M) et temps-dépendante. Cet effet de l'histamine était inhibé par la cimétidine, antagoniste H2 de l'histamine mais non par la diphenhydramine, un antagoniste H1. En outre, le dimparit, un agoniste H2, mais non la 2-pyridyléthylamine, un agoniste H1, a stimulé l'accumulation de cAMP. L'histamine était sans effet sur l'accumulation tissulaire de cAMP ou de cGMP. Parce que le contenu d'histamine dans les glomérules (sime2 times 10-6 M) était bien supérieur aux niveaux circulants d'histamine plasmatique chez l'homme (<10-8 M), nous avons exploré si l'histamine se forme dans le tissu humain normal. L'incubation de glomérules avec 1 mM d'histidine, le précurseur de l'histamine, a entrainé une augmentation des niveaux d'histamine (+ Delta6,08 plusminus 0,5 pmoles/mg protéines, N = 7 reins) alors qu'une chute marquée des niveaux d'histamine était observée dans les tubules (-Delta13,8 plusminus 2,4 pmoles/mg protéines, N = 7 reins). L'augmentation des niveaux d'histamine dans les glomérules a été abolie par la bromocrésine, un inhibiteur de l'histidinedécarboxylase. Ces résultats indiquent que les glomérules humains possèdent des récepteurs H2 pour l'histamine qui médient la stimulation de l'accumulation de cAMP, et que les glomérules sont les sites principaux de production d'histamine dans le rein humain. L'histamine agissart par l'intermédiaire du cAMP pourrait influencer la fonction glomérulaire dans le rein humain.

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