Gut hormones have various physiological functions that include c444ck specifically targeting the brain to regulate appetite. New research suggests that gut hormones can be used to specifically regulate energy homeostasis in humans, and offer a target for anti-obesity drugs. In rodent kidneys (rat, mice, and guinea pigs), CCK has recently been shown by immunohistochemistry to be expressed both in the renal cortex and in the medulla.
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The CCK-B or CCK2 receptor (the “brain” receptor) is the predominant CCK receptor in the brain (67, 71). It is less specific than the CCK1 receptor and binds also non-sulfated CCK, gastrins, and C-terminal fragments such as CCK-5. It has been shown that the gastrin receptor cloned from the stomach (67) and CCK2 receptors are identical (71, 72). The gastrin/CCK2 receptor is expressed also in substantial amounts in pancreatic islet cells in man (73). Designed the expression constructs, purified all the receptor–G complexes, and prepared the final samples for negative staining EM and cryo-EM data collection; Y.D., H.Z., Y.-Y.L., L.L., and H.W.
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A small fragment (SmBiT) was N-terminally fused to a C68-mutated Gγ2 subunit with a 15-amino acid flexible linker. HEK293T cells were seeded in a six-well plate and allowed to grow to 80% confluence before transfection. For measuring Gs signaling, a plasmid mixture consisting of 200 ng LgBiT-inserted Gαs subunit, 1000 ng Gβ1, 1000 ng C68S-mutant SmBiT-fused Gγ2 (C68S), 400 ng test GPCR in 200 μL of Opti-MEM (Gibco) was transiently transfected with PEI. After 1-day transfection, transfected cells were plated onto a 96-well plate treated by cell adherent reagent (Applygen).
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CCK peptides are known to be synthetized in small intestinal endocrine I-cells and cerebral neurons. CCK peptides stimulate pancreatic enzyme secretion and growth, gallbladder contraction, and gut motility, satiety and inhibit acid secretion from the stomach. Moreover, they are major neurotransmitters in the brain and the periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon secretion, and they may act as natriuretic peptides in the kidneys. CCK peptides are derived from proCCK with a C-terminal bioactive YMGWMDFamide sequence, in which the Y-residue is partly O-sulfated.
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- Professors and postdoctoral fellows may apply for a CCK Scholar Grant ranging from $20,000 to $35,000 to help replace half of their salary while they’re on sabbatical, or for time off for research and writing.
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