Ethanol's effect on rat pituitary adrenal axis is prevented by purine metabolic pathway inhibitors

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/kg bodyweight) and high (HE = 2.5 g/kg 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). EtOH at 0-50 mM does not increase the in vitro basal or CRF (10-7 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 (H2O) 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.