gamma-Aminobutyric acid-induced elevation of intracellular calcium concentration in pituitary cells of neonatal rats.
Gamma-aminobutyric acid (GABA) increased intracellular calcium concentration ([Ca2+]i) of newborn rat pituitary cells in suspension measured by the FURA-2 method. The effect of GABA was dose dependent in the range of 0.1-10 microM. This effect diminished with postnatal age as measured at days 2, 14 and 21, and in adult animals. The GABA stimulation was mimicked by muscimol; in contrast, baclofen (up to 100 microM) was ineffective. Picrotoxin, a GABAA antagonist interacting with GABA-activated chloride ionophores, caused a dose-dependent inhibition of the [Ca2+]i elevating effect of 100 microM GABA or muscimol. These observations indicate the involvement of GABAA type receptors. The GABA or muscimol effect on [Ca2+]i was antagonized by nifedipine (10 microM) or verapamil (50 microM), and completely abolished in the presence of 4 mM EGTA (low-calcium medium). The findings indicate the presence of depolarizing GABAA receptors on neonatal rat pituitary cells. It seems very likely that the mechanism by which GABA receptor occupation results in elevated [Ca2+]i is a membrane depolarization by increased Cl- conductance followed by calcium influx through L-type voltage-dependent calcium channels.
Horváth
G
G
Heim Pál Pediatric Hospital, Budapest, Hungary.
Acs
Z
Z
Mergl
Z
Z
Nagy
I
I
Makara
G B
GB
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005260:Female; D016257:Fura-2; D066298:In Vitro Techniques; D009118:Muscimol / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010852:Picrotoxin / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001418:Baclofen; D002118:Calcium; D016257:Fura-2; D009118:Muscimol; D009543:Nifedipine; D010852:Picrotoxin; D011189:Potassium Chloride; D011963:Receptors, GABA-A; D014700:Verapamil; D005680:gamma-Aminobutyric Acid