CCK-58 prolongs the intermeal interval, whereas CCK-8 reduces this interval: Not all forms of cholecystokinin have equal bioactivity

TMEM16B determines cholecystokinin sensitivity of intestinal vagal afferents of nodose neurons

“…With a paucity of chemical receptors in stomach vagal afferents (51), nutrient contents are primarily detected by the proximal and distal intestines (51). Endocrine I cells located in the mucosa of intestine secrete CCK after intake of protein, fat, and amino acids (52) to activate vagal afferents (15,16,45,53,54) and regulate short-term food intake (5,7,9,12,13).…”

“…Its suppressive effect on food intake is reduced in obesity (10,11). Administration of CCK decreases meal size and increases meal duration (5,7,12,13). Conversely, administration of a CCK1 (CCKA) receptor antagonist decreases feelings of fullness and increases meal size in humans (5,14).…”

Role of gastrointestinal hormones in feeding behavior and obesity treatment

“…The major circulating forms are CCK-8, CCK-22, CCK-33, and CCK-58, all having the same attribute, a C-terminal heptapeptide amide sequence for binding [42][43][44]. Although they have the same attribute, not all forms of CCK show equal bioactivity; for example, both CCK-8 and CCK-58 can reduce meal size after administration, but only CCK-58 increases the intermeal interval time, while CCK-8 reduces this interval, as shown in previous studies [45,46]. CCK performs its action through cholecystokinin-1 (CCK1) receptors and/or cholecystokinin-2 (CCK2) receptors [47].…”

Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

“…While the earliest studies utilized natural porcine CCK-33, all more recent studies used synthetic CCK, specifically CCK-8, due to ease of synthesis and inclusion of the minimal fragment with full activity and potency at CCK1R, the carboxyl-terminal heptapeptide-amide. In feeding studies, this peptide has been shown to reproducibly reduce meal size [6], however, its impact on inter-meal interval has been variable, with some studies demonstrating more frequent meals (shortening of inter-meal interval), capable of offsetting the beneficial impact of reduced meal size [23, 24]. It is now appreciated that the dominant form of CCK released into the circulation is a longer form of this hormone with an amino-terminal extension, CCK-58 [25].…”

“…It is now appreciated that the dominant form of CCK released into the circulation is a longer form of this hormone with an amino-terminal extension, CCK-58 [25]. CCK-58 has been consistently shown to not only reduce meal size, but also extend the inter-meal interval [23, 24]. This provides important reassurance that the “ satiation ” effect of CCK (reduced meal size) is not offset by reduced “satiety” (increased meal frequency).…”