Methylamine, but not ammonia, is hypophagic in mouse by interaction with brain Kv1.6 channel subtype.
Ammonia and methylamine (MET) are endogenous compounds increased during liver and renal failure, Alzheimer's disease, vascular dementia and diabetes, where they alter some neurobehavioural functions probably acting as potassium channel blockers. We have already described that potassium channel blockers including tetraethylammonium (TEA), ammonia and MET are hypophagic in mice. Antisense oligonucleotides (aODNs) against Shaker-like Kv1.1 gene abolished the effect of TEA but not of ammonia and MET. The central effects elicited in fasted mice by ammonia and MET were further studied. For MET, an ED(50) value 71.4+/-1.8 nmol mouse(-1) was calculated. The slope of the dose-response curves for these two compounds and the partial hypophagic effect elicited by ammonia indicated a different action mechanism for these amines. The aODNs pretreatments capable of temporarily reducing the expression of all seven known subtypes of Shaker-like gene or to inactivate specifically the Kv1.6 subtype abolished the hypophagic effect of MET but not that of ammonia. Reverse transcription-polymerase chain reaction, Western blot and immunohistochemical results indicate that a full expression in the brain of Kv1.6 is required only for the activity of MET, and confirms the different action mechanism of ammonia and MET.
Pirisino
Renato
R
Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50134 Florence, Italy. renato.pirisino@unifi.it
Ghelardini
Carla
C
Pacini
Alessandra
A
Galeotti
Nicoletta
N
Raimondi
Laura
L
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D051667:Kv1.6 Potassium Channel; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats
C496984:Kcna6 protein, mouse; D051667:Kv1.6 Potassium Channel; D008744:Methylamines; D016376:Oligonucleotides, Antisense; D024642:Potassium Channels, Voltage-Gated; D000641:Ammonia; C027451:methylamine