The FASEB Journal, Vol 9, 815-819, Copyright © 1995 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Glutamate increases cytosolic calcium in GH3 pituitary cells acting via a high-affinity glutamate transporter

C Villalobos and J Garcia-Sancho
Departamento de Bioquimica y Biologia Molecular y Fisiologia, Facultad de Medicina, Universidad de Valladolid, Spain.

Hormone secretion by GH3 pituitary cells is regulated by oscillations 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-glutamate and other acidic amino acids, but not selective excitatory amino acid receptor agonists, increase [Ca2+]i in GH3 cells. Activation by glutamate is blocked by dihydropyridines or removal of extracellular Ca2+ or Na+, but not by tetrodotoxin or excitatory amino acid receptor antagonists. Glutamate 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 GH3 cells by an Na(+)-dependent high-affinity transporter. The half- maximal effect of glutamate on [Ca2+]i was reached at concentrations similar to the Km for the glutamate transporter. Moreover, only those amino acids taken up through this transporter were able to increase [Ca2+]i. We propose that electrogenic entry of Na(+)-glutamate depolarizes the plasma membrane, thus causing an increase of action potentials firing and Ca2+ 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.

This article has been cited by other articles:

				S. L. Ingram and S. G. Amara Arachidonic Acid Stimulates a Novel Cocaine-Sensitive Cation Conductance Associated with the Human Dopamine Transporter J. Neurosci., January 15, 2000; 20(2): 550 - 557. [Abstract] [Full Text] [PDF]

				C. Villalobos, W. J. Faught, and L. S. Frawley Dynamic Changes in Spontaneous Intracellular Free Calcium Oscillations and Their Relationship to Prolactin Gene Expression in Single, Primary Mammotropes Mol. Endocrinol., January 1, 1998; 12(1): 87 - 95. [Abstract] [Full Text]

				M. Chung, C. Teng, M. Timmerman, G. Meschia, and F. C. Battaglia Production and utilization of amino acids by ovine placenta in vivo Am J Physiol Endocrinol Metab, January 1, 1998; 274(1): E13 - E22. [Abstract] [Full Text] [PDF]

				M. J. Barrero, M. Montero, and J. Alvarez Dynamics of [Ca2+] in the Endoplasmic Reticulum and Cytoplasm of Intact HeLa Cells. A COMPARATIVE STUDY J. Biol. Chem., October 31, 1997; 272(44): 27694 - 27699. [Abstract] [Full Text] [PDF]

				R. I. Fonteriz, C. Villalobos, and J. Garcia-Sancho An extracellular sulfhydryl group modulates background Na+ conductance and cytosolic Ca2+ in pituitary cells Am J Physiol Cell Physiol, April 1, 2002; 282(4): C864 - C872. [Abstract] [Full Text] [PDF]