GABA inhibition of somatostatin gene expression in cultured hypothalamic neurones.
GABAA receptors mediate the inhibition of somatostatin release in hypothalamic neurones. To study the possible effect of GABA on somatostatin biosynthesis, somatostatin and preprosomatostatin mRNA levels were evaluated after exposure of hypothalamic neurones to muscimol or bicuculline. Muscimol (50 microM) decreased preprosomatostatin mRNA levels, by 25% after 4 h and 30% after 24 h treatment. Bicuculline (50 microM and 100 microM) increased preprosomatostatin mRNA levels by 1.4 and 1.5 fold after 4 h and by 1.3 and 1.7 fold after 24 h treatment. Somatostatin content was not modified after muscimol or bicuculline exposure. Total DNA content, used to control cellular viability, was not modified under any experimental conditions. Our findings suggest that the GABAergic inhibition of mRNA levels could be a consequence of the GABA inhibition of somatostatin release, thus allowing limited changes in peptide steady-state levels.
Rage
F
F
URA 1197 CNRS, Université de Montpellier II, France.
Jalaguier
S
S
Rougeot
C
C
Tapia-Arancibia
L
L
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D015342:DNA Probes; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000096:biosynthesis* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000199:Actins; D015342:DNA Probes; D011498:Protein Precursors; D012333:RNA, Messenger; D009118:Muscimol; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D004247:DNA; D001640:Bicuculline