title: Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms.
abstract: Dynorphin (Dyn) peptides were previously shown to increase plasma corticotropin (ACTH) in the ovine fetus, but the site of its action remains unclear. In the present study, Dyn A(1-17) was found to stimulate ACTH release from mouse anterior pituitary tumor AtT-20 cells in a dose-dependent manner. Naloxone did not block the effect of Dyn A(1-17) and the selective kappa-opioid receptor agonist U50488H did not stimulate ACTH release. Dyn A(2-17), a degradative peptide fragment that does not bind to opioid receptors, also stimulated ACTH release from AtT-20 cells. Although the nonopioid effects of Dyn have previously been attributed to N-methyl-D-aspartate (NMDA) receptors, the ACTH-releasing effects of Dyn A(1-17) in AtT-20 cells were not affected by co-administration of NMDA receptor antagonist LY235959. The ACTH response to Dyn A(1-17) could not be blocked by alpha-helical CRH (CRH antagonist) and was additive with a maximal stimulatory dose of CRH, suggesting different mechanisms of action. These results show that the release of ACTH by Dyn A(1-17) in AtT-20 cells is not mediated by kappa-opioid receptors or by the NMDA receptor.
authors.affiliation: Department of Pharmacology, Department of Medicine, Weill Medical College of Cornell University, New York, N.Y., USA. pycheng@mail.med.cornell.edu
authors.forename: P Y
authors.initials: PY
authors.lastname: Cheng
authors.forename: A V
authors.initials: AV
authors.lastname: Birk
authors.forename: M C
authors.initials: MC
authors.lastname: Gershengorn
authors.forename: H H
authors.initials: HH
authors.lastname: Szeto
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism / Q000494:pharmacology*; D004723:Endorphins / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*
chemical_list: D004723:Endorphins; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D009294:Narcotics; D010446:Peptide Fragments; D016202:N-Methylaspartate; C026843:dynorphin (1-13); D004399:Dynorphins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C088643:LY 235959