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.