SOMATOSTATIN DESENSITIZATION - LOSS OF THE ABILITY OF SOMATOSTATIN TO INHIBIT CYCLIC-AMP ACCUMULATION AND ADRENOCORTICOTROPIN HORMONE-RELEASE

Addition of somatostatin (SRIF) inhibits corticotropin-releasing factor- and forskolin-stimulated cAMP accumulation and ACTH secretion from mouse anterior pituitary tumor cells (AtT-20/D16-16). Prior exposure of these cells to SRIF reduced the potency of SRIF to inhibit both corticotropin-releasing factor- and forskolin-stimulated cAMP accumulation and ACTH release. This SRIF desensitization is time- and concentration-dependent and reversible. Cross-desensitization to SRIF analogs [D-Trp8SRIF, Tyr''-SRIF and SRIF-28] also occurred whereas SRIF pretreatment did not affect the inhibition by SRIF of 8-bromo-cAMP-stimulated ACTH release or did it affect basal cyclic AMP levels, protein content or phosphodiesterase activity. SRIF can evidently regulate the sensitivity of its own receptor and SRIF desensitization may involve either a down-regulation of SRIF receptors or an uncoupling of these inhibitory receptors from adenylate cyclase.