Multiple mechanisms of somatostatin inhibition of adrenocorticotropin release from mouse anterior pituitary tumor cells.
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 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 three 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 more than one second messenger system.
Reisine
T
T
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology*
D015124:8-Bromo Cyclic Adenosine Monophosphate; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium