Gamma aminobutyric acid regulates glucosensitive neuropeptide Y neurons in arcuate nucleus via A/B receptors.
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.
Muroya
Shinji
S
Department of Physiology, Division of Integrative Physiology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi 329-0498, Japan.
Funahashi
Hisayuki
H
Uramura
Kazuhide
K
Shioda
Seiji
S
Yada
Toshihiko
T
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists; D005947:Glucose / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009478:Neuropeptide Y / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000145:classification / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018755:GABA Agonists; D018756:GABA Antagonists; D009478:Neuropeptide Y; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D001418:Baclofen; D005947:Glucose; D002118:Calcium; D001640:Bicuculline