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    • Ghrelin receptors in non mammals

    2022-07-29

    Ghrelin receptors in non-mammals are reportedly more “complicated/complex and diverse” than in mammals, having additional paralogs and splice variants (Kaiya et al., 2014). Several teleost fish GHS-Rs have been identified; however, functional characterization has been conducted in only a few (see, Kaiya et al., 2013, Kaiya et al., 2014). Most teleost fish possess both GHS-R1a and GHS-R1b, and a limited number of fishes, such as Cyprinoformes and Siluriformes possess a second isoform, GHS-R2a, which is considered to be derived by a whole-genome duplication (WDG) event (see, Kaiya et al., 2013, Kaiya et al., 2014). The two isoforms, GHS-R1a and GHS-R2a, are encoded by separate genes located on different chromosomes, e.g. chromosome 4 and 24, respectively, in zebrafish (Danio rerio) (Howe et al., 2013; Kaiya et al., 2014). The ghrelin/GHS-R system has been established in channel catfish (Ictalurus punctatus). Ghrelin peptide and cDNA encoding precursor protein were isolated from the channel catfish stomach and characterized (Kaiya et al., 2005), with two functional catfish ghrelins identified. The first, designated as “ghrelin,” is a 22-amino MDL 28170 peptide with the third serine residue modified by n-decanoic acid and the carboxyl end of the peptide possessing an amide structure. The second is a Gly-extended, non-amidated 23-amino acid ghrelin, designated as “ghrelin-Gly.” Both catfish ghrelin and ghrelin-Gly function as growth hormone secretagogues in channel catfish, with ghrelin-Gly being the more potent secretagogue (Kaiya et al., 2005). The isolation of channel catfish ghrelin receptors, GHS-R1a, -R1b, and -R2a, was reported four years later (Small et al., 2009). Organization and tissue expression were similar to that reported in other species, and administration of endogenous catfish ghrelin and ghrelin-Gly yielded observable tissue-specific alterations in the expression of both receptor genes. Intrinsic expression of channel catfish GHS-R1a and -1b is the highest in the pituitary, while GHS-R2a is more highly expressed in the Brockmann bodies, the diffuse endocrine pancreas. Together, these results suggest regulatory and functional differences between the two receptors.
    Materials and methods
    Results
    Discussion
    Acknowledgements The authors wish to express our thanks to Monica Wood, Jimmie Warren, Jenny Paul, and Azumi Ooyama for their technical assistance in the conduct of this experiment. This project was partially funded by the United States Department of Agriculture, Agricultural Research Service, Warmwater Aquaculture Research Unit (6066-31000-013-00). Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the U.S. Department of Agriculture and does not imply approval to the exclusion of other products that may be suitable.
    Introduction Growth hormone secretagogues (GHSs) are a class of compounds that stimulate the secretion of growth hormone (GH) by acting on the ghrelin receptor, also known as the growth hormone secretagogue receptor type-1a (GHS-R1a) [1]. This receptor is predominantly found in the hypothalamus and pituitary gland [1] and its secretion occurs through a route disparate from that of growth hormone-releasing hormone (GHRH) [2]. The first GHSs to show GH release in vitro were a series of Met-enkephalin analogues described by Bowers et al. in 1980 [3]. Further development of these analogues led to a hexamer that released GH in vivo in a number of animals [4,5], including humans [6]. This peptide was later termed growth hormone-releasing peptide-6 (GHRP-6), and a number of GHSs were subsequently synthesised in order to find alternatives to recombinant human GH therapy. These encompassed peptides (e.g. GHRP-1 [7], hexarelin [8], KP-102 (later designated GHRP-2) [9]), peptidomimetics (e.g. G-7039 [10] [1-Nal]4G-7039 [11] and ipamorelin [12]), and small molecules (e.g. L-692,429 [13] and MK-0677 [14]). The amino acid sequences of the peptidic GHSs and the structures of the peptidomimetic and small-molecule GHSs are shown in Fig. 1. The endogenous ligand for GHS-R1a is ghrelin, a 28-mer peptide with an n-octanoyl group on the Ser3 side-chain, which was discovered in 1999 [15] and exhibits a multitude of biological activities, such as the regulation of food intake and glucose metabolism [16,17].