Adrenocorticotropin Secretion by Mouse Pituitary Tumor Cells in Culture: The Role of Ca+2in Stimulated and Somatostatin-Inhibited Secretion*

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Abstract
SRIF [somatostatin release-inhibiting factor] inhibits ACTH secretion by AtT20/D16v (D16) mouse pituitary [tumor] cells stimulated by high (50 mM) extracellular concentrations of K+ or by divalent cation ionophores. Although stimulation of ACTH secretion by K+ requires extracellular Ca2+, the response is invariant over medium Ca2+ concentrations of 0.003-1 mM; with Ca2+ concentrations from 1-5 mM there is a dramatic amplification of the secretory response. SRIF at concentrations of 10-8 M completely inhibits the secretory response to K+ at Ca2+ concentrations between 0.2 and 1 mM; with increasing medium Ca2+ above 1 mM there is a progressive attenuation of SRIF-inhibition. At concentrations of 5 mM, Ca2+ alone can serve as an ACTH secretagogue. The ionophore ionomycin stimulates ACTH secretion in a Ca2+-dependent manner with a half-maximal effect at 5 .times. 10-6 M ionomycin. The secretory response to ionomycin and to X537A [lasalocid] is inhibited by at least 50% by SRIF. The secretory response to K+ is accompanied by a rapid and sustained increase in 45Ca2+ uptake, while the ionophores ionomycin, X537A [calcimycin], and A23187 increase Ca2+ efflux. SRIF does not affect Ca2+ movement across D16 cell membranes in response to either K+ or ionophores. An increase in intracellular Ca2+ is an effective stimulus to ATCH secretion by D16 cells and inhibition of ACTH secretion by SRIF is not effected by interference with the stimulus-elicited increase in intracellular Ca2+.