Histamine turnover in the brain of different mammalian species: implications for neuronal histamine half-life.
The turnover of neuronal histamine (HA) in nine brain regions and the spinal cord of the guinea pig and the mouse was estimated and the values obtained were compared with data previously obtained in rats. The size of the neuronal HA pool was determined from the decrease in HA content, as induced by (S)-alpha-fluoro-methylhistidine (alpha-FMH), a suicide inhibitor of histidine decarboxylase. The ratios of neuronal HA to the total differed with the brain region. Pargyline hydrochloride increased the tele-methylhistamine (t-MH) levels linearly up to 2 h after administration in both the guinea pig and the mouse whole brain. Regional differences in the turnover rate of neuronal HA, calculated from the pargyline-induced accumulation of t-MH, as well as in the size of the neuronal HA pool, were more marked in the mouse than in the guinea pig brain. The hypothalamus showed the highest rate in both species. There was a good correlation between the steady-state t-MH levels and the turnover rate in different brain regions. Neither the elevation of the t-MH levels by pargyline nor the reduction of HA by alpha-FMH was observed in the spinal cord, thereby suggesting that the HA present in this region is of mast cell origin. The half-life of neuronal HA in different brain regions was in the range of 13-38 min for the mouse and 24-37 min for the guinea pig, except for HA from the guinea pig hypothalamus, which had an extraordinarily long value of 87 min. These results suggest that there are species differences in the function of the brain histaminergic system.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D007031:Hypothalamus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008761:Methylhistamines / Q000378:metabolism; D008762:Methylhistidines / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D013045:Species Specificity; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution
D008761:Methylhistamines; D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D010293:Pargyline; D006640:Histidine Decarboxylase; C020404:tele-methylhistamine