Plasma CCK levels after food intake and infusion of CCK analogues that inhibit feeding in dogs

Abstract

To determine whether postprandial plasma levels of cholecystokinin (CCK) are sufficient to produce satiety, we compared CCK levels after food intake and administration of CCK analogues that suppress feeding. Seven beagles were adapted to ad libitum access to solid food for 18 h, which was followed by 4 h of food deprivation and a 1-h test session. Plasma CCK increased from 2.7 +/- 0.2 pM before to a maximum of 5.0 +/- 0.7 pM after ingestion of solid food. Intravenous cholecystokinin octapeptide (CCK-8; 0, 50, 100, 200, 400, 800 pmol.kg-1.h-1), caerulein (0, 25, 50, 100, 200, 400 pmol.kg-1.h-1), and [Thr4,Nle7]CCK-9 (0, 25, 50, 100, 200, 400 pmol.kg-1.h-1), at a rate of 1 dose/day given 15 min before feeding and during a 45-min feeding period, caused similar dose-dependent suppression of feeding at 200 pmol.kg-1.h-1 and greater. On separate days blood samples for peptide assay were collected during infusion of scalar ascending doses of CCK-8 or [Thr4,Nle7]CCK-9 (0, 25, 50, 100, 200, 400 pmol.kg-1.h-1) or caerulein (0, 16.7, 50, and 150 pmol.kg-1.h-1), with each dose being administered for 30 min. Peptide levels were highly correlated with dose (r = 0.94, 0.87, and 0.95 for CCK-8, caerulein, and [Thr4,Nle7]CCK-9, respectively). Peptide levels after minimal effective doses for suppression of feeding were 59 +/- 6, 54 +/- 7, and 70 +/- 5 pM for CCK-8, caerulein, and [Thr4,Nle7]CCK-9. These results suggest that postprandial plasma levels of CCK are not sufficient to produce satiety.