Abstract
The peptide hormone cholecystokinin (CCK) exerts a wide range of digestive and CNS-related physiological signaling via CCK receptors in brain and gut. There is very limited information available on these receptors in Atlantic salmon. The aim of this study was to characterize CCK receptors in gut and brain of salmon. We have identified and cloned one CCK-1 receptor and duplicates of CCK-2 receptor in salmon. The phylogenetic analysis indicates the existence of one common ancestor gene for all CCK receptors. CCK-1R mRNA is highly expressed in pancreas followed by midgut, hindgut, gallbladder, and stomach indicating an involvement in pancreatic regulation and gallbladder contractions. CCK-2R1/gastrin mRNA is expressed at high levels in midgut and at relatively low levels in stomach, gallbladder, and pancreas. We postulate CCK-2R1/gastrin receptor to have gastrin-related functions because of its distribution and abundance in gastro-intestinal (GI) tissues. CCK-2R2 is relatively abundant in brain but has low expression levels in gut tissues supporting the hypothesis for involvement in the gut-brain signaling. Major functional motifs and ligand interaction sites in salmon are conserved with that of mammals. This information will be instrumental for comparative studies and further targeting receptor activation and selectivity of biological responses of CCK in salmon.
Highlights
Cholecystokinin (CCK) is a key regulatory peptide hormone that serves a wide variety of physiological actions
This study reports the identification of both subtypes of cholecystokinin receptors (CCK-1R and CCK-2R)
The open reading frames (ORFs) of CCK-2R1/gastrin cloned from midgut cDNA consisted of 1608 bases and comprised a CDS of 1359 bases encoding for a putative protein of 453 amino acids
Summary
Cholecystokinin (CCK) is a key regulatory peptide hormone that serves a wide variety of physiological actions It is a prototype of a class of agents known as brain-gut peptides, functioning both as neuropeptide and gut hormone. CCK exerts its biological actions by binding to specific G-protein-coupled receptors (GPCRs) known as CCK-1R and CCK-2R (formerly termed as CCK-AR and CCKBR, respectively). These receptors differ in their distribution and their affinities for natural agonists. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society
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