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.
Zivadinovic
Dragoslava
D
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA.
Tomić
Melanija
M
Yuan
Davy
D
Stojilkovic
Stanko S
SS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006062:Gonadotropins / Q000096:biosynthesis; D013006:Growth Hormone / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D051381:Rats; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006062:Gonadotropins; D007295:Inositol Phosphates; D007476:Ionophores; D010908:Pituitary Hormones, Anterior; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat; D015759:Ionomycin; D007986:Luteinizing Hormone; D013006:Growth Hormone; D000242:Cyclic AMP; D002118:Calcium