ABSTRACT
Significance of the formation of 4-dimethylamino-3-hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-on e (AM-3-CH2OH) for the metabolism of AM was examined quantitatively in rats. Although urinary excretion of AM-3-CH2OH accounted for only 0.7% to the dose, incubation of AM in the isolated hepatocyte system resulted in the formation of 9% of AM-3-CH2OH. Furthermore, metabolic disappearance of AM-3-CH2OH in the same system was fast, indicating the properties of an intermediate metabolite. These results suggested that the metabolic pathways via AM-3-CH2OH are very important in the metabolism of AM.
Subject(s)
Aminopyrine/metabolism , Aminopyrine/analogs & derivatives , Aminopyrine/biosynthesis , Animals , Hydroxylation , Kinetics , Rats , Rats, Inbred StrainsABSTRACT
The relationship between cyclic AMP production and the response of isolated canine parietal cells to histamine has been examined. Histamine increased cyclic AMP generation, and this effect correlated with histamine stimulation of oxygen consumption and aminopyrine accumulation. Metiamide inhibited histamine-stimulated cyclic AMP generation and oxygen consumption in a parallel fashion. At concentrations below 100 microM, isobutyl AMP production and oxygen consumption in a similar fashion. However, with IMX above 100 microM, histamine caused no further increases in oxygen consumption, despite markedly enhanced cyclic AMP generation. Neither carbachol nor gastrin increased cyclic AMP production beyond that produced by IMX alone, and the combinations of histamine and carbachol and of histamine and gastrin produced no greater cyclic AMP generation than produced by histamine. These findings support a close relationship between cyclic AMP production and the action of histamine but not of carbachol or gastrin on isolated parietal cells. The mechanisms underlying the potentiating interactions between histamine, carbachol, and gastrin involve step(s) beyond stimulation of cyclic AMP generation.
