Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms.
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.
Cheng
P Y
PY
Department of Pharmacology, Department of Medicine, Weill Medical College of Cornell University, New York, N.Y., USA. pycheng@mail.med.cornell.edu
Birk
A V
AV
Gershengorn
M C
MC
Szeto
H H
HH
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*
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