Effects of guanine nucleotides on CNS neuropeptide receptors

The effect of nucleotides on central nervous system neuropeptide receptor binding was investigated. The guanine nucleotides, guanosine-5'-triphosphate and guanylyl-5'-imidodiphosphate, significantly inhibited the binding of radiolabeled vasoactive intestinal polypeptide but not that of [Tyr4]bombesin to rat brain membranes. Vasoactive intestinal polypeptide binding was inhibited by guanine nucleotides in a dose-dependent manner. Using a 20 microM dose, 60% of the specific vasoactive intestinal polypeptide binding was inhibited by guanylyl-5'-imido-diphosphate, which was more potent than guanosine-5'-triphosphate, whereas other nucleotides were not effective. This reduction in binding was a consequence of lower affinity of the receptor for vasoactive intestinal polypeptide, which in turn resulted from an increased rate of dissociation.