ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract— A new method has been developed for the separation of histamine and its metabolites after intracisternal injection of [3H]histamine into the rat brain, involving solvent extraction and subsequent thin-layer chromatography.The effect of graded doses of the MAO inhibitors deprenil and pargyline, which at relatively low doses inhibit preferentially the B form (phenethylamine deaminating) of the enzyme, and clorgyline, which mainly inhibits the A form (serotonin, noradrenaline and dopamine deaminating) on the brain levels of intracisternally injected [3H]histamine and its labelled metabolites was studied and compared to MAO A and B activity as determined with the substrates serotonin and phenethylamine, respectively. In addition, the time-course of the effects of a single dose of pargyline (50mg/kg subcutaneously) was investigated. No [3H]imidazoleacetic acid could be detected in any of the control or treated animals. [3H]Histamine accounted for 9–12% of the total extracted radioactivity and this was not altered significantly by pretreatment with any of the MAO inhibitors up to high doses, at which both MAO A and B activities were completely inhibited.In the controls, 40–43% of the total extracted radioactivity was [3H]methylhistamine and 28–30% was [3H]methylimidazoleacetic acid. Deprenil and pargyline caused [3H]methylhistamine levels to increase in a dose-dependent manner up to about 150% of control levels and those of [3H]methylimida-zoleacetic acid to decrease concomitantly to about 10% of control levels. Clorgyline in doses up to 10 mg/kg subcutaneously (s.c.) had no effect on the levels of these two metabolites. The dose-response curves of the effects of deprenil and pargyline on [3H]methylimidazoleacetic acid levels were congruent with those of the MAOI effects on MAO B activity and not with those on MAO A activity.Pargyline (50 mg/kg s.c.) had a long lasting effect on the accumulation of [3H]methylhistamine and [3H]methylimidazoleacetic acid. Recovery occurred within 21 days, and the half-lives observed were 5.3 and 5.6 days, respectively. This compares well to the half-life for the recovery of MAO B activity reported earlier after the same dose of pargyline (5.5 days).These results suggest that methylhistamine is metabolized selectively by MAO B in rat brain. Moreover, the fact that clorgyline, at doses where phenethylamine deamination is already considerably inhibited, did not affect the deamination of methylhistamine, suggests that the latter is an even more selective substrate for MAO B than phenethylamine itself.Therefore, small doses of deprenil (0.3–3 mg/kg s.c.) or pargyline (1–3 mg/kg) can be used to influence histamine catabolism without interfering with catecholamine or serotonin deamination.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1977.tb10719.x
Permalink
