Site and mechanism of action of dynorphin A-(1–13) andN-methyl-d-aspartate on ACTH release in fetal sheep

Autor: I. Ross Young, David W. Walker, Dunli Wu, Yi Soong, Hazel H. Szeto, Laura Nardo
Rok vydání: 2002
Předmět:
Zdroj: American Journal of Physiology-Endocrinology and Metabolism. 282:E1301-E1307
ISSN: 1522-1555
0193-1849
DOI: 10.1152/ajpendo.00527.2001
Popis: Dynorphin A (Dyn A) stimulates the release of ACTH in fetal sheep, a response that involves N-methyl-d-aspartate (NMDA) receptors but not the secretogogues corticotropin-releasing hormone or arginine vasopressin. We now find that neither Dyn A-(1–13) (0.5 mg/kg, iv) nor NMDA (4 mg/kg, iv) elicits ACTH release in postnatal lambs. This led us to hypothesize that Dyn A-(1–13) and NMDA might act to release placental ACTH. However, the ability of Dyn A-(1–13), NMDA, and the κ-opioid receptor agonist U-50488H (1 mg/kg, iv) to release ACTH was lost after either fetal hypophysectomy ( n = 4) or hypothalamo-pituitary disconnection ( n = 4). These results indicate that neither the placenta nor the fetal pituitary is the site of action for these agonists and suggest a hypothalamic or suprahypothalamic site of action. Furthermore, the release of ACTH by Dyn A-(1–13) and NMDA was abolished after pretreatment with indomethacin, suggesting that they might cause the release of a prostanoid, possibly from the placenta, that subsequently acts at the hypothalamus or serves as a permissive factor in the action of Dyn A-(1–13) and NMDA at the hypothalamus.
Databáze: OpenAIRE