G-PROTEIN REGULATION OF ADENYLATE-CYCLASE ACTIVITY IN RAT PROSTATIC MEMBRANES AFTER CHRONIC ETHANOL INGESTION

BACKGROUND. The possibility that long-term ethanol ingestion might alt er either vasoastive intestinal peptide (VIP) content, VIP binding to membrane receptors, G-protein levels or adenylate cyclase activity in rat prostate was tested, as ethanol produces serious alterations in th e hypothalamic-pituitary-gonadal axis and several modifications on dif ferent elements on signal transduction pathways in other systems. METH ODS. Prostatic membranes from control and ethanol-treated (for 4 weeks ) rats were used to study adenylate cyclase stimulation as well as for the immunodetection of stimulatory (alpha(s)) and inhibitory (alpha(i 1-2)) G-protein subunits. Studies on VIP binding and cross-linking to receptors were performed using [I-125]VIP. Prostatic VIP content was e stimated by radioimmunoassay. GTPase activity was quantified by measur ing the amount of (32)Pi released from [gamma-P-32]Gm. RESULTS. Chroni c ethanol ingestion resulted in an increased presence of VIP in the ra t prostate without any change on the VIP receptor/effector system in t his gland. By contrast, the basal adenylate cyclase activity as well a s the dose-dependent stimulation of this enzyme by either the nonhydro lyzable Gm analogue Gpp(NH)p or the beta-adrenergic agonist isoprotere nol were enhanced in prostatic membranes after ethanol intake. Moreove r, an increase in the content of G-protein subunits (alpha(s) and alph a(i1-2)) was observed without any change in GTPase activity in this co ndition. These modifications were accompanied by a significant decreas e in rat prostate weight and, consequently, the height of the secretor y epithelium in this gland. CONCLUSIONS. Considering the role of VIP i n the mechanisms of secretion and cell proliferation in the prostate, the observed increases in the prostatic content of VIP and G-protein s ubunits make conceivable that VIP and cAMP signal transduction could b e involved in the atrophy of the rat prostate and in the alterations i n the composition of seminal fluid that appear in the alcoholic syndro me. Prostrate 36:226-234, 1998. (C) 1998 Wiley-Liss, Inc.