Gamma aminobutyric acid regulates glucosensitive neuropeptide Y neurons in arcuate nucleus via A/B receptors

Gamma aminobutyric acid (GABA) is localized in neuropeptideY (NPY) neurons of the hypothalamic arcuate nucleus (ARC). We examined regulation of ARC NPY neurons by GABA. Light and electron microscopic immunohistochemistry confirmed that GABA-containing nerve terminals contacted NPY-containing neurons in the ARC. Lowering glucose (I mM) increased cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in isolated ARC neurons that were immunoreactive to NPY. The [Ca 2+ ] i increases were inhibited by GABA, the γ-aminobutyric acid type A receptor (GABA A ) agonist muscimol and the γ-aminobutyric acid type B receptor (GABA B ) agonist baclofen. Neither the GABA A antagonist bicuculline nor the GABA B antagonist CGP35348 counteracted the GABA inhibition when applied alone, but did so when applied together. These results indicate that GABA regulates ARC glucose-sensitive NPY neurons via GABA A and GABA B receptors, which could function to attenuate the orexigenic NPY pathway when it is not beneficial.