Ethanol's Effect on Rat Pituitary Adrenal Axis is Prevented by Purine Metabolic Pathway Inhibitors

Abstract

This study investigated the in vitro dose effects of ethanol (EtOH), adenosine (ADO), and urate (URA) on the basal and CRF stimulated ACTH production of pituitary tissue culture (PTC). Furthermore, the effects of low (LE = 0.5 g k g bodyweight) and high (HE = 2.5 g k g bodyweight) concentrations of EtOH were tested in rats on plasma ACTH and corticosterone concentration (PCC), with or without the following ADO metabolic pathway inhibitors: 6-mercaptopurine (6MP) (salvage pathway) and purpurogallin (PPG) (xanthine dehydrogenase).M) stimulated ACTH secretion in PTC; in fact doses up to 20 mM tended to be inhibitory. ADO significantly increased only basal ACTH secretion whereas URA increased both basal and CRF-stimulated ACTH secretion.Pretreatment with PPG or 6MP + PPG significantly increased both in vivo ACTH and PCC over control values in rats. HE versus LE significantly increased ACTH and PCC in the control (H,O) and 6MP pretreated groups whereas in the PPG pretreated animals, only ACTH was increased significantly by HE. However, combined pretreatment with 6MP + PPG prevented the effect of HE on ACTH and PCC. The current experiment suggests that purine metabolism is involved in ethanol's effect on the hypothalamic-pituitary-adrenal axis.

Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol

“…No study has yet reported on the plasma concentration of purpurogallin after its administration. However, some biological activities of orally administrated purpurogallin have been observed in laboratory animals (Mammalia) [33][34][35]. The results of those studies indicate that purpurogallin is absorbed in mammalian bodies through the gastrointestinal track and then manifest its activities.…”

Intervention at the Level of the Neuroendocrine–Immune Axis and Postoperative Pneumonia Rate in Long-term Alcoholics

“…Ethanol, morphine, and ketoconazole might have influenced the HPA axis at different levels. Low-dose ethanol inhibits signal transduction between the hypothalamus and pituitary (21). In a clinical study, ethanol infusion significantly decreased cortisol levels in early withdrawal (36).…”

“…Ethanol at a low concentration (0.5 g/kg/d) has immunestimulating effects in an experimental model, and also increases viral elimination from liver tissue (20). In addition, ethanol at this low dose was reported to inhibit corticotropin-releasing hormone-mediated adrenocorticotropic hormone (ACTH) secretion (21). Morphine acts as a powerful inhibitor of the HPA axis by reducing ACTH and cortisol response to corticotropinreleasing hormone in the activated stress axis (22,23).…”