ANALYSIS OF VASOACTIVE-INTESTINAL-PEPTIDE RECEPTORS AND THE G-PROTEINREGULATION OF ADENYLYL-CYCLASE IN SEMINAL-VESICLE MEMBRANES FROM STREPTOZOTOCIN-DIABETIC RATS

The present report describes the status of the vasoactive intestinal p eptide (VIP) receptor/effector system of signal transduction in semina l vesicle from streptozotocin (STZ)-treated rats. STZ-treatment modifi ed the binding parameters of the high-affinity sites for VIP in semina l vesicle: 0.78 a 0.10 and 2.54 +/- 0.30 nM for the dissociation const ant (K-d) in control and diabetic rats, respectively; 0.07 +/- 0.01 an d 0.15 +/- 0.03 pmol VIP/mg protein for the maximum binding capacity ( B-max) in control and diabetic rats, respectively. It was associated w ith a reduced potency of VIP on the stimulation of adenylyl cyclase ac tivity in the diabetic state (ED(50) = 64.0 +/- 20.0 nM) as compared t o control (ED(50) = 9.5 +/- 4.3 nM). In contrast, the stimulatory effe cts of GTP, Gpp[NH]p and forskolin on the enzyme activity were not mod ified in diabetic rats. The levels of G-protein subunits in rat semina l vesicle were studied by immunoblot of alpha(s) and alpha(i) subunits : whereas alpha(1)-subunit levels did not vary, those corresponding to alpha(s) subunit decreased after STZ treatment. In diabetic rats, low concentrations of Gpp[NH]p failed to inhibit forskolin-stimulated ade nylyl cyclase activity, suggesting the absence of functional G(i) in t his condition. In conclusion, present results show a decrease in the s ensitivity of the VIP receptor/effector system in seminal vesicle memb ranes from STZ-treated rats suggesting a physiopathological role for V IP in the seminal neuropathy observed in diabetes.