Somatostatin inhibits multireceptor stimulation of cyclic AMP formation and corticotropin secretion in mouse pituitary tumor cells.

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Abstract
The AtT-20/D16-16 mouse pituitary tumor cell secretes ACTH in response to corticotropin-releasing factor (CRF), (-)-isoproterenol, and vasoactive intestinal peptide (VIP). These responses are associated with a rapid increase in cAMP formation. Somatostatin (SRIF) markedly decreases the stimulatory effect of CRF, (-)-isoproterenol, and VIP on both cAMP formation and immunoreactive ACTH secretion. Forskolin and cholera toxin, adenylate cyclase activators, also stimulate cAMP formation and ACTH secretion in AtT-20 cells, and these responses are all inhibited by SRIF. The ACTH secretory responses to melittin and to the calcium ionophore A23187 [calcimycin], neither of which increases cAMP in AtT-20 cells, were not inhibited by SRIF. SRIF did not affect the binding of a tritiated .beta.-adrenergic receptor antagonist to AtT-20 membranes nor did it decrease basal cAMP formation even in the presence of excess phosphodiesterase inhibitor, indicating that the reduction of cAMP levels by SRIF did not involve either an interference with .beta.-adrenergic agonist binding to receptors or stimulation of cAMP degradation. The inhibition of CRF-, (-)-isoproterenol-, and VIP-stimulated ACTH secretion by SRIF may be regulated by its inhibitory action on adenylate cyclase.