GAMMA-AMINOBUTYRIC ACID-INDUCED ELEVATION OF INTRACELLULAR CALCIUM-CONCENTRATION IN PITUITARY-CELLS OF NEONATAL RATS

Gamma-aminobutyric acid (GABA) increased intracellular calcium concent ration ([Ca2+]i) of newborn rat pituitary cells in suspension measured by the FURA-2 method. The effect of GABA was dose dependent in the ra nge of 0.1-10 muM.This effect diminished with postnatal age as measure d at days 2, 14 and 21, and in adult animals. The GABA stimulation was mimicked by muscimol; in contrast, baclofen (up to 100 muM) was ineff ective. Picrotoxin, a GABA(A) antagonist interacting with GABA-activat ed chloride ionophores, caused a dose-dependent inhibition of the [Ca2 +]i elevating effect of 100 muM GABA or muscimol. These observations i ndicate the involvement of GABA(A) type receptors. The GABA or muscimo l effect on [Ca2+]i was antagonized by nifedipine (10 muM) or verapami l (50 muM), and completely abolished in the presence of 4 mM EGTA (low -calcium medium). The findings indicate the presence of depolarizing G ABA(A) receptors on neonatal rat pituitary cells. It seems very likely that the mechanism by which GABA receptor occupation results in eleva ted [Ca2+]i is a membrane depolarization by increased Cl- conductance followed by calcium influx through L-type voltage-dependent calcium ch annels.