Guanyl nucleotide regulation of vasoactive intestinal peptide interaction with rat liver membranes.

This study shows the regulatory role of guanyl nucleotides on vasoactive intestinal peptide (VIP) interaction with rat liver plasma membranes. The binding of 125I-VIP to the membranes was partially inhibited by GTP and the GTP-analog Gpp(NH)p in a dose-dependent manner. This effect was mainly due to a dramatic increase of the dissociation rate of the complex tracer-membranes in the presence of guanyl nucleotides. The specificity of the binding inhibition was assessed from the lack of action of the other purine nucleotides tested. VIP stimulated cyclic AMP production in liver plasma membranes in the range 10(-10) -- 3 x 10(-7) M. Half-maximal stimulation was observed at 3 x 10(-10) M and maximal stimulation (4-fold basal value) at 10(-9) M VIP. Both GTP and Gpp(NH)p potentiated VIP-stimulated cyclic AMP production since the effect of nucleotide plus VIP was greater than the sum of the effects produced by the two agents separately. Therefore, guanyl nucleotides simultaneously inhibit the binding of VIP to its receptors and potentiate the stimulatory effect of VIP on adenylate cyclase activity in rat liver plasma membranes.