Cell-type specific messenger functions of extracellular calcium in the anterior pituitary

Abstract

Calcium can serve not only as an intracellular messenger, but also as an extracellular messenger controlling the gating properties of plasma membrane channels and acting as an agonist for G protein-coupled Ca2+-sensing receptors. Here we studied the potential extracellular messenger functions of this ion in anterior pituitary cells. Depletion and repletion of the extracellular Ca2+ concentration ([Ca2+]e) induced transient elevations in the intracellular Ca2+ concentration ([Ca2+]i), and elevations in [Ca2+]e above physiological levels decreased [Ca2+]i in somatotrophs and lactotrophs, but not in gonadotrophs. The amplitudes and duration of [Ca2+]i responses depended on the [Ca2+]e and its rate of change, which resulted exclusively from modulation of spontaneous voltage-gated Ca2+ influx. Changes in [Ca2+]e also affected GH and PRL secretion. The PRL secretory profiles paralleled the [Ca2+]i profiles in lactotrophs, whereas GH secretion was also stimulated by [Ca2+]e independently of the status of voltage-gated Ca2+ influx. [Ca2+]e modulated GH secretion in a dosedependent manner, with EC50 values of 0.75 and 2,25 mM and minimum secretion at about 1.5 mM. In a parallel experiment, cAMP accumulation progressively increased with elevation of [Ca2+]e, whereas inositol phosphate levels were not affected. These results indicate the cell type-specific role of [Ca2+]e in the control of Ca2+ signaling and secretion.