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

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 Ca(2+)-sensing receptors. Here we studied the potential extracellular messenger functions of this ion in anterior pituitary cells. Depletion and repletion of the extracellular Ca(2+) concentration (Ca(2+)]e) induced transient elevations in the intracellular Ca(2+) concentration (Ca(2+)]i), and elevations in Ca(2+)]e above physiological levels decreased Ca(2+)]i in somatotrophs and lactotrophs, but not in gonadotrophs. The amplitudes and duration of Ca(2+)]i responses depended on the Ca(2+)]e and its rate of change, which resulted exclusively from modulation of spontaneous voltage-gated Ca(2+) influx. Changes in Ca(2+)]e also affected GH and PRL secretion. The PRL secretory profiles paralleled the Ca(2+)]i profiles in lactotrophs, whereas GH secretion was also stimulated by Ca(2+)]e independently of the status of voltage-gated Ca(2+) influx. Ca(2+)]e modulated GH secretion in a dose-dependent manner, with EC(50) 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 Ca(2+)]e, whereas inositol phosphate levels were not affected. These results indicate the cell type-specific role of Ca(2+)]e in the control of Ca(2+) signaling and secretion.