Direct effects of 3,4-dihydroxybutanoic acid gamma-lactone and 2,4,5-trihydroxypentanoic acid gamma-lactone on lateral and ventromedial hypothalamic neurons

The mechanism of central actions of endogenous sugar acids, 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP) which have been newly identified as satiety and hunger substances respectively, was investigated. Intracellular recordings were made from neurons in the lateral hypothalamic area (LHA) of rats and ventromedial hypothalamic nucleus (VMH) of guinea pigs, brain areas referred to as feeding and satiety centers, respectively. The LHA neurons hyperpolarized by 3,4-DB show no change in membrane input resistance while the depolarized VMH neurons are associated with an increase in membrane resistance. The mechanisms related to the action of 3,4-DB on these hypothalamic neurons are similar to those in case of glucose on the glucose-sensitive neuron in the LHA and the glucoreceptor neuron in the VMH. 2,4,5-TP depolarized LHA neurons but hyperpolarized VMH neurons with a decrease in the membrane resistance. Our findings indicate that 3,4-DB and 2,4,5-TP have reciprocal effects on each LHA and VMH neurons, with regard to neuronal excitability.