EFFECT OF ADENOSINE AND ITS METABOLITES ON THE HYPOTHALAMOPITUITARY-ADRENAL AXIS

Adenosine (ADO) plays a key role in maintaining the energy charge of t he cell and has been shown in vivo to stimulate hypothalamo-pituitary- adrenocortical (HPA) activity. The question arises as to whether these effects are related exclusively to ADO and/or its metabolic product(s ). Therefore, the present study was designed to test the in vivo effec t of ADO and its phosphorylated or deaminated derivatives on plasma co rticosterone concentration (PCC) in rats. ATP, ADP, AMP, ADO, inosine (INO), hypoxanthine (HYP), xanthine (XAN), and urate (URA) in solution s (40 mu mol/100 g of metabolic body weight) were injected intraperito neally, then 30 min later the animals were decapitated and the plasma samples were collected for corticosterone radioimmunoassay (RIA). Dose response curves for ADO and URA as well as a time course response for plasma URA and PCC following ADO administration were obtained. In add ition, the effect of URA on the adrenocorticotrophic hormone (ACTH) se cretion of AtT-20 pituitary cells in culture was determined. The resul ts showed that not only ADO bur the adenine nucleotides (AMP, ADP, ATP ) and also the deaminated end-products (INO, XAN, URA) significantly i ncreased PCC. HYP did not have any significant effect. The dose depend ent effects of ADO and URA on PCC were significantly and highly correl ated. URA stimulated ACTH secretion significantly in vitro in a dose-d ependent manner, suggesting that ADO metabolites increase PCC via ACTH release. The possibility that ADO metabolites, principally URA, could be important signals for the HPA axis is discussed.