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.
Cioni
Laura
L
Department of Pharmacology, University of Florence, Italy.
De Siena
Gaetano
G
Ghelardini
Carla
C
Sernissi
Olivia
O
Alfarano
Chiara
C
Pirisino
Renato
R
Raimondi
Laura
L
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008744:Methylamines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism
D001067:Appetite Depressants; D006146:Guanidines; D008744:Methylamines; D024642:Potassium Channels, Voltage-Gated; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing); C004479:pimagedine