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 (Δ + 100% to + 265%) in a dose- (10-6 to10-4 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 H1 agonist 2-pyridylethylamine stimulated cAMP accumulation. Histamine had no effect on cAMP or cGMP accumulation in tubules. Because the content of histamine (≃ 2 x 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 (+ Δ6.08 ± 0.5 pmoles/mg protein, N = 7 kidneys) while a marked drop in histamine levels was observed in tubules (-Δ13.8 ± 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.
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