Multiple Mechanisms of Somatostatin Inhibition of Adrenocorticotropin Release from Mouse Anterior Pituitary Tumor Cells

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Abstract
The release of ACTH from a clonal cell line of the mouse anterior pituitary (AtT-20/D16-16) can be stimulated by forskolin, 8-bromo-cAMP, and K+. SRIF [somatostatin] and its structurally related analogs are very potent inhibitors of the ACTH release response to these secretagogues. The potency of SRIF, its analogs, and somatostatin-28 to inhibit stimulated ACTH release is relatively the same for each of these 3 secretagogues. The mechanisms by which SRIF regulates the secretion of ACTH can be differentiated by various pharmacological manipulations. Pretreatment of AtT-20 cells with SRIF (10-7 M) desensitizes SRIF''s inhibition of forskolin but not K+ or 8-bromo-cAMP-stimulated ACTH release. Pertussis toxin pretreatment abolishes SRIF''s inhibition of forskolin-stimulated ACTH release but not SRIF''s inhibition of the ACTH release response to K+ or 8-bromo-cAMP. In contrast, increasing the calcium concentration in the medium reduces SRIF''s inhibition of K+ but not forskolin or 8-bromo-cAMP-stimulated ACTH release. These results suggest that SRIF regulates ACTH release from AtT-20 cells through multiple mechanisms. If SRIF acts through a single receptor to produce its effects on ACTH release, then the data imply that the SRIF receptor is coupled to > 1 2nd messenger system.