Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms

Dynorphin (Dyn) peptides were previously shown to increase plasma corticotr opin (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. Na loxone did not block the effect of Dyn A(1-17) and the selective kappa-opio id receptor agonist U50488H did not stimulate ACTH release. Dyn A(2-17), a degradative peptide fragment that does not bind to opioid receptors, also s timulated ACTH release from AtT-20 cells. Although the nonopioid effects of Dyn have previously been attributed to N-methyl-D-aspartate (NMDA) recepto rs, the ACTH-releasing effects of Dyn A(1-17) in AtT-20 cells were not affe cted by co-administration of NMDA receptor antagonist LY235959. The ACTH re sponse to Dyn A(1-17) could not be blocked by alpha-helical CRH (CRH antago nist) and was additive with a maximal stimulatory dose of CRH, suggesting d ifferent 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. Copyright (C) 2000 S. Karger AG, Baser.