Proadrenomedullin N-terminal 20 peptide inhibits adrenocorticotropin secretion from cultured pituitary cells, possibly via activation of a potassium channel

Preproadrenomedullin is processed into at least two biologically active pep tides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAM P), Both peptides are hypotensive; however, they exert this action via diff ering mechanisms. In pituitary cells in culture, both basal and releasing f actor-stimulated adrenocorticotropin (ACTH) secretion is inhibited by AM. H ere we report that basal, but not stimulated, ACTH secretion from cultured rat pituitary cells is also inhibited by PAMP, The effect is dose-related, occurs in a physiologically relevant dose range that is similar to that of AM, and is blocked by the potassium channel blocker, glybenclamide, The fai lure of glybenclamide to inhibit AM's effects on ACTH secretion indicates t hat in pituitary, as in other tissues, these two products of the same proho rmone can exert similar biologic activity, although via differing mechanism s.