Bullfrog Ghrelin Is Modified by n-Octanoic Acid at Its Third Threonine Residue

Hiroyuki Kaiya, Masayasu Kojima, Hiroshi Hosoda, Aya Koda, Kazutoshi Yamamoto, Yasuo Kitajima, Masaru Matsumoto, Yoshiharu Minamitake, Sakae Kikuyama, Kenji Kangawa

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    137 Citations (Scopus)

    Abstract

    We have identified the amphibian ghrelin from the stomach of the bullfrog. We also examined growth hormone (GH)-releasing activity of this novel peptide in both the rat and bullfrog. The three forms of ghrelin identified, each comprised of 27 or 28 amino acids, possessed 29% sequence identity to the mammalian ghrelins. A unique threonine at amino acid position 3 (Thr 3) in bullfrog ghrelin differs from the serine present in the mammalian ghrelins; this Thr3 is acylated by either n-octanoic or n-decanoic acid. The frog ghrelin-28 has a complete structure of GLT (O-n-octanoyl)FLSPAD-MQKIAERQSQNKLRHGNM; the structure of frog ghrelin-27 was determined to be GLT(O-n-octanoyl)FLSPAD-MQKIAERQSQNKLRHGN; frog ghelin-27-C10 possessed a structure of GLT(O-n-decanoyl)FLSPADMQKIAERQSQNKLRHGN. Northern blot analysis demonstrated that ghrelin mRNA is predominantly expressed in the stomach. Low levels of gene expression were observed in the heart, lung, small intestine, gall bladder, pancreas, and testes, as revealed by reverse transcription polymerase chain reaction analysis. Bullfrog ghrelin stimulated the secretion of both GH and prolactin in dispersed bullfrog pituitary cells with potency 2-3 orders of magnitude greater than that of rat ghrelin. Bullfrog ghrelin, however, was only minimally effective in elevating plasma GH levels following intravenous injection into rats. These results indicate that although the regulatory mechanism of ghrelin to induce GH secretion is evolutionary conserved, the structural changes in the different ghrelins result in species-specific receptor binding.

    Original languageEnglish
    Pages (from-to)40441-40448
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume276
    Issue number44
    DOIs
    Publication statusPublished - 2001 Nov 2

    ASJC Scopus subject areas

    • Biochemistry

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  • Cite this

    Kaiya, H., Kojima, M., Hosoda, H., Koda, A., Yamamoto, K., Kitajima, Y., Matsumoto, M., Minamitake, Y., Kikuyama, S., & Kangawa, K. (2001). Bullfrog Ghrelin Is Modified by n-Octanoic Acid at Its Third Threonine Residue. Journal of Biological Chemistry, 276(44), 40441-40448. https://doi.org/10.1074/jbc.M105212200