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 ĸ-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 α-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 ĸ-opioid receptors or by the NMDA receptor.