Visualization of gamma-aminobutyric acid A receptors on proopiomelanocortin-producing neurons in the rat hypothalamus.

Abstract

It has recently been shown that gamma-aminobutyric acid (GABA) and central-type benzodiazepine receptor agonists inhibit the expression of the POMC gene and the release of POMC-derived peptides from hypothalamic neurons. To determine whether the inhibitory effect of GABA could be accounted for by a direct action on POMC neurons, we investigated the localization of the beta 1-subunit of the GABAA-benzodiazepine-receptor complex in the arcuate nucleus. Using a monoclonal antibody raised against a synthetic fragment of the beta 1-subunit, we demonstrate the presence of GABAA receptor on POMC neurons. The proportion of POMC neurons that exhibit immunoreactivity for the beta 1-subunit of the GABAA receptor was not significantly different in the posterior portion (73.0-76.0%) and anterior portion (61.3-62.7%) of the arcuate nucleus. The data also revealed that in the arcuate nucleus, a majority of neurons that were immunostained by the antibody to the beta 1-subunit were not POMC positive. The present results support the concept that GABAA and central-type benzodiazepine receptor agonists exert a direct inhibitory action on POMC neurons. The data also indicate the existence of subsets of POMC neurons within the arcuate nucleus.