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), adenos ine (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 Et OH were tested in rats on plasma ACTH and corticosterone concentration (PCC ), with or without the following ADO metabolic pathway inhibitors: 6-mercap topurine (6MP) (salvage pathway) and purpurogallin (PPG) (xanthine dehydrog enase). EtOH at 0-50 mM does not increase the in vitro basal or CRF (10(-7) M) stim ulated ACTH secretion in PTC; in fact doses up to 20 mM tended to be inhibi tory. ADO significantly increased only basal ACTH secretion whereas URA Inc reased both basal and CRF-stimulated ACTH secretion. Pretreatment with PPG or 6MP + PPG significantly increased both in vivo ACT H 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. Howev er, combined pretreatment with 6MP + PPG prevented the effect of HE on ACTH and PCC, The current experiment suggests that purine metabolism is involve d in ethanol's effect on the hypothalamic-pituitary-adrenal axis.