Glutamate increases cytosolic calcium in GH3 pituitary cells acting via a high-affinity glutamate transporter
Villalobos, C.; García-Sancho, J.
FASEB Journal 9(9): 815-819
1995
ISSN/ISBN: 0892-6638 PMID: 7601345 Document Number: 454847
Hormone secretion by GH-3 pituitary cells is regulated by oscillations of the cytosolic Ca-2+ concentration ((Ca-2+)-i), which are driven by electrical activity and modulated by hypothalamic releasing factors. We find that micromolar concentrations of L-glutamate and other acidic amino acids, but not selective excitatory amino acid receptor agonists, increase (Ca-2+)-i in GH-3 cells. Activation by glutamate is blocked by dihydropyridines or removal of extracellular Ca-2+ or Na+, but not by tetrodotoxin or excitatory amino acid receptor antagonists. Glutamate also accelerated the entry of Mn-2+ used as a Ca-2+ surrogate for Ca-2+ channels. L-Glutamate and other acidic amino acids were taken up into GH-3 cells by an Na+-dependent high-affinity transporter. The half-maximal effect of glutamate on (Ca-2+)-i was reached at concentrations similar to the K-m for the glutamate transporter. Moreover, only those amino acids taken up through this transporter were able to increase (Ca-2+)-i. We propose that electrogenic entry of Na+-glutamate depolarizes the plasma membrane, thus causing an increase of action potentials firing and Ca-2+ entry through voltage-gated channels. Our results suggest that glutamate may cooperate to the modulation of pituitary hormone secretion by an unconventional mechanism involving a high-affinity glutamate transporter rather than excitatory amino acid receptors.