TY - JOUR
T1 - Catabolism of histamine in the isolated glomeruli and tubules of the rat kidney
AU - Abboud, H. E.
N1 - Funding Information:
The work was supported through Veterans Administration Research Funds. Preliminary results of this work were published as abstracts in Clin Res 29: 166A, 1981, and Kidney mt 21:249, 1982. The author thanks Dr. M. Dunn for his continuous support during the course of these experiments, and Dr. J. Sedor for reviewing the manuscript. The technical assistance of Miss M. Grunberger and the secretarial assistance of J. Smart and L. Polacek are acknowledged.
PY - 1983
Y1 - 1983
N2 - Histamine alters renal hemodynamics including the glomerular microcirculation, and histamine receptors are present in rat glomeruli. We have recently shown that isolated rat glomeruli, but not cortical tubules, incubated with the histamine substrate L-histidine synthesize histamine. This study explores the catabolic pathways of histamine in isolated glomeruli and cortical tubules of the rat kidney. Glomeruli and cortical tubules were incubated with radiolabelled histamine, and the products were separated on thin layer chromatography (TLC). Glomeruli predominantly catabolized histamine to acid metabolites of the diamine oxidase (histaminase) pathway, imidazole acetic acid and ribosylimidazole acetic acid, and to a lesser extent to the inactive methylation product, Nτ-methylhistamine (7.5% vs. 2.5%). Tubules on the other hand catabolized histamine to Nτ-methylhistamine and to a lesser degree to acid metabolites (7.6% vs. 2.3%). The methyl donor S-Adenosyl-methionine (SAM) (10-4 M) markedly enhanced the production of Nτ-methylhistamine in both glomeruli and tubules (Δ + 600%) but had no effect on the production of acid metabolites. In the presence of equimolar concentrations of SAM, tubules continued to methylate histamine to a greater extent than glomeruli (46.0% vs. 18%). In both glomeruli and tubules, the diamine oxidase inhibitor, amino-guanidine, abolished the production of acid metabolites while amodiaquine and pyrilamine, inhibitors of the methylation pathway, markedly reduced the production of Nτ-methylhistamine. In addition, in the presence of SAM, tubules catabolized nonlabelled histamine to a greater extent than glomeruli. These studies show that tubules have a greater capacity than glomeruli to degrade histamine and that histamine is differentially catabolized in these segments. A major pathway of histamine catabolism in glomeruli results in the formation of biologically active products.
AB - Histamine alters renal hemodynamics including the glomerular microcirculation, and histamine receptors are present in rat glomeruli. We have recently shown that isolated rat glomeruli, but not cortical tubules, incubated with the histamine substrate L-histidine synthesize histamine. This study explores the catabolic pathways of histamine in isolated glomeruli and cortical tubules of the rat kidney. Glomeruli and cortical tubules were incubated with radiolabelled histamine, and the products were separated on thin layer chromatography (TLC). Glomeruli predominantly catabolized histamine to acid metabolites of the diamine oxidase (histaminase) pathway, imidazole acetic acid and ribosylimidazole acetic acid, and to a lesser extent to the inactive methylation product, Nτ-methylhistamine (7.5% vs. 2.5%). Tubules on the other hand catabolized histamine to Nτ-methylhistamine and to a lesser degree to acid metabolites (7.6% vs. 2.3%). The methyl donor S-Adenosyl-methionine (SAM) (10-4 M) markedly enhanced the production of Nτ-methylhistamine in both glomeruli and tubules (Δ + 600%) but had no effect on the production of acid metabolites. In the presence of equimolar concentrations of SAM, tubules continued to methylate histamine to a greater extent than glomeruli (46.0% vs. 18%). In both glomeruli and tubules, the diamine oxidase inhibitor, amino-guanidine, abolished the production of acid metabolites while amodiaquine and pyrilamine, inhibitors of the methylation pathway, markedly reduced the production of Nτ-methylhistamine. In addition, in the presence of SAM, tubules catabolized nonlabelled histamine to a greater extent than glomeruli. These studies show that tubules have a greater capacity than glomeruli to degrade histamine and that histamine is differentially catabolized in these segments. A major pathway of histamine catabolism in glomeruli results in the formation of biologically active products.
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U2 - 10.1038/ki.1983.190
DO - 10.1038/ki.1983.190
M3 - Article
C2 - 6417393
AN - SCOPUS:0021073786
VL - 24
SP - 534
EP - 541
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 4
ER -