Abstract Cholecystokinin receptor (CCKR), an important recognition receptor for the gastrointestinal hormone cholecystokinin (CCK) in the endocrine system, plays a crucial role in regulating immune responses in mammals. In this study, a novel cholecystokinin receptor ( Ci CCKR) was identified from the grass carp Ctenopharyngodon idella . Similar to other reported CCKR proteins, Ci CCKR features seven transmembrane helical domains, an ERY motif located in transmembrane region III, and a NPIIY motif found in transmembrane region VII. Expression profiling indicated that Ci CCKR was primarily expressed in the brain, with a lower level of expression in the intestine. Phylogenetic analysis revealed that Ci CCKR belonged to the fish cluster and showed the closest relationship to Megalobrama amblycephala . In vivo injection experiments demonstrated that Ci CCK and Ci CCKR exhibited a strong response to stimulation with Aeromonas hydrophila , Aeromonas veronii , and Muramyl Dipeptide (MDP), with expression levels significantly up‐regulated in the intestines of grass carp. In cases of intestinal inflammation induced by MDP, CCK can significantly decrease the expression levels of inflammatory factors ( Ci TNF‐α, Ci IL‐1β, Ci IL‐8) and the Ci PepT1/ Ci NOD2 pathway ( Ci PepT1, Ci NOD2, Ci RIP2), while expression levels of the genes in the Ci CCKR pathway ( Ci CCKR, Ci GNAS) are significantly up‐regulated. In vitro and in vivo experiments indicated that knocking down Ci CCKR and treating with its inhibitor proglumide effectively regulated MDP‐induced intestinal inflammation by activating the Ci PepT1/ Ci NOD2 pathway. Overall, these findings suggested that Ci CCKR may play a critical role in the intestinal immune response to bacterial challenges.
Peng et al. (Mon,) studied this question.