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 peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP). Both peptides are hypotensive; however, they exert this action via differing mechanisms. In pituitary cells in culture, both basal and releasing factor-stimulated adrenocorticotropin (ACTH) secretion is inhibited by AM. Here 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 failure of glybenclamide to inhibit AM's effects on ACTH secretion indicates that in pituitary, as in other tissues, these two products of the same prohormone can exert similar biologic activity, although via differing mechanisms.
Samson
W K
WK
Department of Physiology, University of North Dakota School of Medicine, Grand Forks 58202, USA. wsamson@mail.med.und.nodak.edu
Murphy
T C
TC
Resch
Z T
ZT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D053607:Adrenomedullin; D000818:Animals; D002478:Cells, Cultured; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D010455:Peptides; D015221:Potassium Channels; D011506:Proteins; D053607:Adrenomedullin; D000255:Adenosine Triphosphate; D000324:Adrenocorticotropic Hormone; D005905:Glyburide