A novel endogenous sugar acid depolarizes ventromedial hypothalamic neurons in vitro.
2-Buten-4-olide (2-B-4-O) has been identified in the serum of fasted rats and proved to act as a feeding suppressant. The effect of 2-B-4-O on neurons in the ventromedial hypothalamic (VMH) nucleus was investigated with intracellular recordings in brain slice preparations of rats. 2-B-4-O, applied by perfusion (0.1-10 mM) or drops (50-100 mM), dose dependently depolarized 30% of the VMH neurons tested. The depolarization by 2-B-4-O application persisted after complete elimination of synaptic inputs during perfusion with Ca2+-free/high-Mg2+ solution. The depolarization, accompanied by a decrease in membrane conductance, reversed polarity around -95 mV and was dependent on extracellular K+ concentration. The VMH neurons depolarized by 2-B-4-O had some specific electrophysiological properties corresponding with those of glucoreceptor neurons. The results suggest that 2-B-4-O directly excites VMH neurons, presumed to be glucoreceptor neurons, by decreasing K+ conductance, and this effect may participate in the feeding suppressive action of 2-B-4-O.
Fukuda
A
A
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Oomura
Y
Y
Plata-Salamán
C R
CR
Minami
T
T
Ito
C
C
D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005663:Furans / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology*
D005663:Furans; C004511:butenolide; D015107:4-Butyrolactone