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

J. R. Sedor; H. E. Abboud

doi:10.1038/ki.1984.148

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

J. R. Sedor, H. E. Abboud

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Abstract

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.

Original language	English (US)
Pages (from-to)	144-152
Number of pages	9
Journal	Kidney international
Volume	26
Issue number	2
DOIs	https://doi.org/10.1038/ki.1984.148
State	Published - 1984
Externally published	Yes

ASJC Scopus subject areas

Nephrology

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10.1038/ki.1984.148

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title = "Actions and metabolism of histamine in glomeruli and tubules of the human kidney",

abstract = "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.",

author = "Sedor, {J. R.} and Abboud, {H. E.}",

note = "Funding Information: Preliminary results of this work were published in abstract form in Clin Res 31 :44lA, 1983. The work was supported by a grant-in-aid from the American Heart Association, Northeast Ohio Affiliate, and through Veterans Administration Research Funds to Dr. H. E. Abboud. Dr. J. Sedor is a fellow of the Kidney Foundation of Ohio. The authors thank Mr. C. Williams and the personnel at the Organ Preservation Laboratory at the Cleveland Clinic Foundation and the Urology Staff at the Veterans Administration for providing the kidneys, J. Murray and A. Huang for technical assistance, and Mrs. L. Polacek and Mrs. J. Smart for typing assistance.",

year = "1984",

doi = "10.1038/ki.1984.148",

language = "English (US)",

volume = "26",

pages = "144--152",

journal = "Kidney International",

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T1 - Actions and metabolism of histamine in glomeruli and tubules of the human kidney

AU - Sedor, J. R.

AU - Abboud, H. E.

N1 - Funding Information: Preliminary results of this work were published in abstract form in Clin Res 31 :44lA, 1983. The work was supported by a grant-in-aid from the American Heart Association, Northeast Ohio Affiliate, and through Veterans Administration Research Funds to Dr. H. E. Abboud. Dr. J. Sedor is a fellow of the Kidney Foundation of Ohio. The authors thank Mr. C. Williams and the personnel at the Organ Preservation Laboratory at the Cleveland Clinic Foundation and the Urology Staff at the Veterans Administration for providing the kidneys, J. Murray and A. Huang for technical assistance, and Mrs. L. Polacek and Mrs. J. Smart for typing assistance.

PY - 1984

Y1 - 1984

N2 - 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.

AB - 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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DO - 10.1038/ki.1984.148

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

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