Catabolism of histamine in the isolated glomeruli and tubules of the rat kidney.
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, N tau-methylhistamine (7.5% vs. 2.5%). Tubules on the other hand catabolized histamine to N tau-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 N tau-methylhistamine in both glomeruli and tubules (delta + 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 N tau-methylhistamine. In addition, in the presence of SAM, tubules catabolized nonlabelled histamine to a greater extent than glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000655:Amodiaquine / Q000494:pharmacology; D000818:Animals; D002855:Chromatography, Thin Layer; D006146:Guanidines / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008761:Methylhistamines / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006146:Guanidines; D007093:Imidazoles; D008761:Methylhistamines; D000655:Amodiaquine; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing); D011738:Pyrilamine; C005954:imidazoleacetic acid; C004479:pimagedine