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.
D000818:Animals; D001839:Bombesin / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018004:Receptors, Bombesin; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D006150:Guanine Nucleotides; D018004:Receptors, Bombesin; D011964:Receptors, Gastrointestinal Hormone; D017981:Receptors, Neurotransmitter; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D001839:Bombesin