Calcitonin gene-related peptide stimulates adenylate cyclase activation via a guanine nucleotide-dependent process in rat liver plasma membranes

Akinori Yamaguchi, Tsutomu Chiba, Toshiyuki Yamatani, Tetsuya Inui, Tomoyuki Morishita, Akira Nakamura, Seizo Kadowaki, Masaaki Fukase, Takuo Fujita

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    Abstract

    To evaluate the functional relationship between the liver calcitonin gene-related peptide (CGRP) receptor and guanine nucleotide-binding proteins, we investigated the effects of nucleotides not only on adenylate cyclase activation by CGRP, but also on 125I-[Tyr°]rat CGRP binding to rat liver plasma membranes. In the presence of GTP, rat CGRP stimulated adenylate cyclase activity in a dose-dependent manner in rat liver plasma membranes, and this effect was reduced in the absence of GTP. Salmon calcitonin also enhanced adenylate cyclase activation in the presence of GTP, but only in higher concentrations. On the other hand, guanine nucleotides not only decreased 125I-[Tyr°]rat CGRP binding to rat liver plasma membranes, but also accelerated the dissociation of label binding, and the removal of Mg2+ from incubation medium attenuated this inhibitory action of GTP on 125I-[Tyr°]rat CGRP binding to membranes. Scatchard analysis of the data revealed that the reduction of 125I-[Tyr°]rat CGRP binding by GTP was due to the decrease in binding affinity without a significant change in binding capacity. These findings lead us to conclude that binding of CGRP to its receptors activates adenylate cyclase in rat liver plasma membranes via a guanine nucleotide-dependent process, suggesting the involvement of guanine nucleotide-binding stimulatory protein in the action of CGRP.

    Original languageEnglish (US)
    Pages (from-to)2591-2596
    Number of pages6
    JournalEndocrinology
    Volume123
    Issue number5
    DOIs
    StatePublished - Jan 1 1988

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    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Yamaguchi, A., Chiba, T., Yamatani, T., Inui, T., Morishita, T., Nakamura, A., Kadowaki, S., Fukase, M., & Fujita, T. (1988). Calcitonin gene-related peptide stimulates adenylate cyclase activation via a guanine nucleotide-dependent process in rat liver plasma membranes. Endocrinology, 123(5), 2591-2596. https://doi.org/10.1210/endo-123-5-2591