Location: Warmwater Aquaculture Research UnitTitle: Characterization of a third ghrelin receptor, GHS-R3a, in channel catfish reveals novel expression patterns and a high affinity for homologous ligand
|SMALL, BRIAN - University Of Idaho|
|HIROYUKI, KAIYA - National Cardiovascular Center Research Institute|
|BLEDSOE, JACOB - University Of Idaho|
Submitted to: Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2018
Publication Date: 3/1/2019
Citation: Small, B., Quiniou, S., Hiroyuki, K., Bledsoe, J.W., Musungu, B.M. 2019. Characterization of a third ghrelin receptor, GHS-R3a, in channel catfish reveals novel expression patterns and a high affinity for homologous ligand. Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology. 229:1-9.
Interpretive Summary: The peptide ghrelin is a hormone that regulates food intake and energy use in animals. Ghrelin, and its actions on growth hormone are of particular importance to researchers working to enhance channel catfish growth and feed efficiency to improve global competitiveness. In the present study we identified a ghrelin receptor, called GHS-R3a, that is unique to fish. Tissue expression and regulation differ from those for the two previously known GHS-R genes (-R1a and -R2a). We found that GHS-R3a binds particularly well to catfish ghrelin hence maybe a key regulator of growth and feed intake in catfish. As such, GHS-R3a is being looked at as a possible marker in a selective breeding program for growth and fillet yield.
Technical Abstract: A novel third channel catfish growth hormone secretagogue (ghrelin) receptor, GHS-R3a, gene was characterized. Identification and analysis of the genomic organization of channel catfish GHSR-3a revealed differences in exon/intron structure relative to the previously published GHS-R1a and GHS-R2a sequences. Amino acid sequence alignment of catfish GHS-R3a with -R1a and -R2a revealed 48 and 52% sequence identity, respectively. Phylogenetic analysis predicted a new clade of GHS-R3a receptors found only in fish, with representation in the teleost infradivisions Osteoglossomorpha, Clupeomorpha, and Euteleostei. In functional analyses, homologous catfish ghrelin increased intracellular Ca2+ concentration in human embryonic kidney (HEK) 293 cells stably expressing catfish GHS-R3a. On the contrary, intracellular Ca2+ concentration was unaffected by treatment with the synthetic growth hormone secretagogues GHRP-6 and hexarelin. Realtime PCR results indicated high expression of GHS-R3a in the brain and gonads, demonstrating tissue specificity among the catfish GHS-Rs. The effects of fasting and refeeding on all three ghrelin receptors were evaluated in catfish brain, pituitary, stomach, and Brockman bodies. Most notably, GHS-R3a was the only receptor observed to significantly increase (2.9 – 6.3-fold) in brain, pituitary, and stomach within 4 days of fasting (P < 0.05). Stomach GHS-R1a also increased (P < 0.05) after 4 days; however, GHS-R2a was only elevated in brain and pituitary after refeeding for 1 week. Expression of all three ghrelin receptors were elevated (P < 0.05) in the Brockmann bodies after 2 weeks of fasting and returned to prefasting levels following refeeding. Together with the previously published characterization of GHS-R1a and -R2a, these results establish three functional ghrelin receptors, each altered by energy state, in channel catfish and add to the growing body of information on GHS-R evolution and function.