Activity and expression of semicarbazide-sensitive benzylamine oxidase in a rodent model of diabetes: interactive effects with methylamine and alpha-aminoguanidine

Previous data indicate that methylamine injection in fasted healthy mice produced a hypophagic effect dependent of neuronal K(v)1.6 channels expression and increased by alpha-aminoguanidine, an inhibitor of semicarbazide-sensitive benzylamine oxidase enzymes mainly involved in amine degradation. In the present work we have investigated: 1) the level of expression and activity of the semicarbazide-sensitive benzylamine oxidase; 2) the effect of methylamine alone and in the presence of alpha-aminoguanidine on food intake of genetic obese and type II diabetes mice (the db/db mice). Db/db mice showed higher levels of semicarbazide-sensitive benzylamine oxidase activities in adipose tissue and in plasma than their lean counterpart (db/db(+) mice). Methylamine (30-75 microg, i.c.v.) showed similar hypophagic effects in obese and lean mice consistently with the levels of neuronal K(v)1.6 found in both animal strains. Alpha-aminoguandine (50 mg/kg, i.p.) increased methylamine (i.c.v.) hypophagia in both obese and lean mice and only in obese mice when methylamine was given i.p. These results suggest a crucial role of semicarbazide-sensitive benzylamine oxidase activity in controlling methylamine hypophagia in hyperphagic diabetic mice.