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pros ‐Methylimidazoleacetic Acid in Rat Brain: Its Regional Distribution and Relationship to Metabolic Pathways of Histamine
Author(s) -
Prell George D.,
Khandelwal Jai K.,
Hough Lindsay B.,
Green Jack Peter
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb09156.x
Subject(s) - histamine , medicine , endocrinology , metabolite , probenecid , catabolism , pargyline , histidine decarboxylase , chemistry , biology , metabolism , serotonin , histidine , biochemistry , amino acid , receptor
pros ‐Methylimidazoleacetic acid (p‐MIAA; 1‐methylimidazole‐5‐acetic acid), an isomer of the histamine metabolite, tele ‐methylimidazoleacetic acid (t‐MIAA), is present in brain and CSF. Its relationship to histamine synthesis and catabolism was assessed in brains of rats. p‐MIAA distribution in brain regions was heterogeneous although the concentrations in regions with the highest (hypothalamus) and the lowest (medulla‐pons) levels differed less than fourfold. There was no significant correlation between the regional distributions of p‐MIAA with those of histamine or its metabolites. pros ‐Methylhistidine (1 g/kg, i.p.) produced a 20‐fold increase in mean levels of p‐MIAA and up to a 50‐fold increase in levels of pros ‐methylhistamine (p‐MH), a putative intermediate; levels of histamine and its metabolites were unaltered. l ‐Histidine (1 g/kg, i.p.) or α‐fluoromethylhistidine (100 mg/kg, i.p.), the irreversible inhibitor of histamine synthesis, did not alter the levels of p‐MIAA in brain. Like the levels of t‐MIAA, the levels of p‐MIAA were unaltered after probenecid administration. Contrary to its effects in lowering t‐MIAA levels, pargyline (75 mg/kg, i.p.) produced a slight rise in levels of p‐MIAA in all regions. These findings suggest that, in brain, the metabolic pathways of histamine are independent of pathways that generate p‐MIAA. Further, since brain is capable of p‐MH formation, its use as an internal standard in analytical methods merits caution.