Suppression and potentiation of 5-hydroxytryptophan-induced hypoglycaemia by alpha-monofluoromethyldopa: correlation with the accumulation of 5-hydroxytryptamine in the liver.
Experiments were done to examine whether the accumulation of 5-hydroxytryptamine (5-HT) in the liver is responsible for the hypoglycaemia induced in mice by 5-hydroxytryptophan (5-HTP) and lipopolysaccharides (LPS). (+/-)-alpha-Monofluoromethyldopa (FMD), a potent irreversible inhibitor of aromatic amino acid decarboxylase, suppressed the 5-HTP-induced accumulation of 5-HT in the liver at a dose of 2 mg kg-1 or more, but potentiated the accumulation at lower dose of 0.4 mg kg-1. Corresponding to these effects, the hypoglycaemic response was prevented by the higher doses of FMD and potentiated by the lower dose. These contrasting effects of FMD were explicable by the amounts of 5-HTP entering the liver. In contrast, FMD did not prevent either the hypoglycaemia or the accumulation of 5-HT in the liver induced by LPS. These results further support the hypothesis that the accumulation of 5-HT in the liver is causally related to the hypoglycaemia induced by 5-HTP and indicate that the LPS-induced 5-HT accumulation in the liver is not derived from stimulation of 5-HT synthesis. It is still not clear whether the accumulation of 5-HT in the liver is involved in the hypoglycaemic response to LPS.
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002230:Carbidopa / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D012701:Serotonin / Q000378:metabolism*
D001786:Blood Glucose; D008070:Lipopolysaccharides; D012701:Serotonin; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D006916:5-Hydroxytryptophan; D002262:Carboxy-Lyases; D002230:Carbidopa