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George H. Greeley, Evidence for Intelligent Design in Gastrointestinal Endocrinology: Identification of Novel Cholecystokinin/Gastrin-Like Peptides in the Nematode Caenorhabditis elegans, Endocrinology, Volume 149, Issue 6, 1 June 2008, Pages 3184–3186, https://doi.org/10.1210/en.2008-0371
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Many studies have demonstrated that cholecystokinin (CCK)/gastrin peptides have a long evolutionary history. The existence of CCK/gastrin-like peptides, first identified in the mammalian small intestine and stomach, was demonstrated throughout the chordates including the tunicates, which are the lowest chordate subphylum, and the arthropods (insects, arachnids, and crustaceans).
In this issue of Endocrinology, Janssen and co-workers (1), by means of a reverse pharmacology strategy, isolate and characterize two novel CCK/gastrin-like neuropeptides, called NLP-12, as endogenous ligands for CCK receptors (CKR-2a/2b) from the nematode, Caenorhabditis elegans. NLP-12 peptides show a high degree of sequence similarity with the vertebrate CCK/gastrin peptides and the arthropod sulfakinins. In addition, they demonstrate that NLP-12 peptides are recognized by a CCK-specific antibody, confirming structural similarities with the CCK/gastrin and sulfakinin sequences. NLP-12 peptides are not sulfated and have a very limited neuronal expression. NLP-12 peptides stimulate digestive enzyme secretion and fat storage, two biological activities associated with CCK/gastrin and sulfakinin peptides. Interestingly, NLP-12 peptides do not seem to exert a satiety effect. Discovery of the NLP-12 peptides indicates that the CCK/gastrin ligand-CCK1R/2R receptor signaling pathway had evolved before the divergence of protostomes and deuterostomes, and more importantly, the NLP-12-CKR-2a/2b axis represents the most ancient equivalent of the mammalian vertebrate CCK/gastrin-receptor signaling system.
