Cholecystokinin-58 is more potent in inhibiting food intake than cholecystokinin-8 in rats.
BACKGROUND
Several cholecystokinin (CCK) forms have been detected in plasma, but most studies on food intake investigated the effects of CCK-8 only. Recently, it has been demonstrated that CCK-58 is the only endocrine-active form of CCK in rats.


METHODS
CCK-58 was synthesized with a peptide synthesizer using FMOC chemistry and CCK-58 effects on food intake were compared to CCK-8 in rats.


RESULTS
Both CCK-58 and CCK-8 inhibited food intake in a dose-dependent manner and were equally potent at 30 min. CCK-58 showed a prolonged inhibition of food intake compared to CCK8 at the higher dose tested (7 nmol/kg), inhibiting food intake also at 60 min, and cumulative food intake was inhibited for up to 210 min by CCK-58.


CONCLUSIONS
CCK-58 has the same potency in inhibiting food intake as CCK-8 in rats, but inhibits food intake longer. This might be due to its tertiary structure resulting in a delayed plasma degradation or a prolonged binding at the CCK receptor. As CCK-58 is the major CCK form in the gut wall and possibly in the circulating blood in humans, the effects of CCK on food intake might have been underestimated in the past.
Department of General and Transplantation Surgery, University Hospital, University of Tübingen, Germany. joerg.glatzle@med.uni-tuebingen.de
Joerg
J
Glatzle
Helen E
HE
Raybould
Markus A
MA
Kueper
Joseph R
JR
Reeve
Tilman T
TT
Zittel
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*
C038823:cholecystokinin 58; D002766:Cholecystokinin; D012844:Sincalide