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

ABSTRACT

Gamma aminobutyric acid (GABA) is localized in neuropeptide Y (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 (1 mM) increased cytosolic Ca2+ concentration ([Ca2+]i) in isolated ARC neurons that were immunoreactive to NPY. The [Ca2+]i increases were inhibited by GABA, the gamma-aminobutyric acid type A receptor (GABAA) agonist muscimol and the gamma-aminobutyric acid type B receptor (GABAB) agonist baclofen. Neither the GABAA antagonist bicuculline nor the GABAB 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 GABAA and GABAB receptors, which could function to attenuate the orexigenic NPY pathway when it is not beneficial.