GLUTAMATE INCREASES CYTOSOLIC CALCIUM IN GH(3) PITUITARY-CELLS ACTINGVIA A HIGH-AFFINITY GLUTAMATE TRANSPORTER

Hormone secretion by GH(3) pituitary cells is regulated by oscillation s of the cytosolic Ca2+ concentration ([Ca2+](i)), which are driven by electrical activity and modulated by hypothalamic releasing factors. We find that micromolar concentrations of L-gIutamate and other acidic amino acids, but not selective excitatory amino acid receptor agonist s, increase [Ca2+](i) in GH(3) cells. Activation by glutamate is block ed by dihydropyridines or removal of extracellular Ca2+ or Na+, but no t by tetrodotoxin or excitatory amino acid receptor antagonists. Gluta mate mate also accelerated the entry of Mn2+ used as a Ca2+ surrogate for Ca2+ channels. L-Glutamate and other acidic amino acids were taken up into GH(3) cells by an Na+-dependent high-affinity transporter. Th e half-maximal effect of glutamate [Ca2+](i) was reached at concentrat ions similar to the K-m for the glutamate transporter. Moreover, only those amino acids taken up through this transporter were able to incre ase [Ca2+](i). We propose that electrogenic entry of Na+-glutamate dep olarizes the plasma membrane, thus causing an increase of action poten tials firing and Ca2+ entry through voltage-gated channels. Our result s suggest that glutamate may cooperate to the modulation of pituitary hormone secretion by an unconventional mechanism involving a high-affi nity glutamate transporter rather than excitatory amino acid receptors .