Effects of chronic ethanol ingestion on the vasoactive intestinal peptide receptor-effector system from rat seminal vesicle membranes

We studied the modifications of the vasoactive intestinal peptide (VIP) rec eptor/effector system from the rat seminal vesicle after chronic ethanol in gestion. Ethanol treatment resulted in a decreased height of the secretory epithelium of seminal vesicle as well as in a weight loss of this gland. Th ese morphological changes were accompanied by an increase of immunoreactive vasoactive intestinal peptide (VIP) levels and a decrease of the stimulato ry effect of VIP adenylate cyclase activity in the seminal vesicle. The los s of sensitivity of the enzyme to VIP was conceivably related to a decrease in the affinity of VIP receptors rather than to a decrease in their number . The changes in the affinity of the VIP receptors were accompanied with a lower sensitivity of VIP binding to GTP, which suggest an uncoupling betwee n the receptor and the transductor molecules. However, chronic exposure to ethanol did not modify either the levels of G-protein subunits (alpha(s) an d (alpha(i1/2)) or the GTPase activity from seminal vesicle membranes. More over, ethanol feeding did not affect adenylate cyclase activity stimulated by forskolin or by Gpp(NH)p, Thus, ethanol-induced changes in the sensitivi ty of adenylate cyclase to VIP appear to be attributed to an alteration in the VIP-receptor/G-protein interphase rather than in the G-protein/adenylat e cyclase connection.