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

It has been accepted for decades that "all forms of cholecystokinin (CCK) have equal bioactivity," despite accumulating evidence to the contrary. To challenge this concept, we compared two feeding responses, meal size (MS, 10% sucrose) and intermeal interval (IMI), in response to CCK-58, which is the major endocrine form of CCK, and CCK-8, which is the most abundantly utilized form. Doses (0, 0.1, 0.5, 0.75, 1, 3 and 5 nmol/kg) were administered intraperitoneally over a 210-min test to Sprague Dawley rats that had been food-deprived overnight. We found that (1) all doses of CCK-58, except the lowest dose, and all doses of CCK-8, except the lowest two doses, reduced food intake more than vehicle did; (2) at two doses, 0.75 and 3 nmol/kg, CCK-58 increased the IMI, while CCK-8 failed to alter this feeding response; and (3) CCK-58, at all but the lowest two doses, increased the satiety ratio (IMI between first and second meals (min) divided by first MS (ml)) relative to vehicle, while CCK-8 did not affect this value. These findings demonstrate that the only circulating form of CCK in rats, CCK-58, prolongs the IMI more than CCK-8, the peptide generally utilized in feeding studies. Taken together, these results add to a growing list of functions where CCK-8 and CCK-58 express qualitatively different bioactivities. In conclusion, the hypothesis that "all forms of cholecystokinin (CCK) have equal bioactivity" is not supported.

The stomach and/or upper duodenum contain sites of action that control meal size and intermeal interval length by exogenous rat gastrin releasing peptide.

The site(s) of action that control the reduction of food intake in response to the amphibian skin peptide bombesin (Bn) has been determined to be the area supplied by the celiac artery (CA), i.e., the stomach and the upper duodenum. Here, we investigated the gastrointestinal site(s) of action which controls meal size (MS) (normal rat chow) and intermeal interval length (IMI) by the mammalian homologues of Bn gastrin releasing peptides (GRP-10, GRP-27 and GRP-29, 0.01, 0.05, 0.1, 0.2 and 0.5 nmol/kg) infused in the CA, the cranial mesenteric artery (CMA, supplying the small and large intestine), the femoral artery (FA, control) and the portal vein (PV, draining the gastrointestinal tract, control) in freely fed rats immediately prior to the onset of the dark cycle. We found that (1) GRP-29 (0.05, 0.1, 0.2 and 0.5 nmol/kg) and GRP-27 (0.2 and 0.5 nmol/kg) in the CA and GRP-29 (0.5 nmol/kg) in the CMA reduced the MS relative to saline, (2) GRP-29 (0.1, 0.2 and 0.5 nmol/kg) and GRP-27 (0.2 and 0.5 nmol/kg) in the CA prolonged the IMI, (3) GRP-29 (0.1, 0.2 and 0.5 nmol/kg) in the CA and GRP-29 (0.5 nmol/kg) in the CMA increased the satiety ratio (SR, IMI/MS - the amount of food consumed per a given unit of time) and (4) neither peptide nor route showed any effect on the second MS. These results support an upper gastrointestinal site of action for MS and IMI length by GRP-27 and GRP-29, which is most likely the stomach and/or the duodenum.

Intravenous infusion of gastrin-releasing peptide-27 and bombesin in rats reveals differential effects on meal size and intermeal interval length.

We have previously shown that the intraperitoneal (i.p.) administration of gastrin-releasing peptide-27 (GRP-27) or bombesin (BN) (at 0.21, 0.41 and 1.03nmol/kg) reduces meal size (MS) and prolongs the intermeal interval (IMI). Here, we hypothesized that the intravenous (i.v.) administration of the same doses of GRP-27 and BN will be as effective as the i.p. administration in evoking these feeding responses. To test this hypothesis, we administered GRP-27 and BN i.v. and measured first MS (10% sucrose), IMI, satiety ratio (SR, IMI/MS) and second MS in overnight food-deprived but not water-deprived male Sprague Dawley rats. We found that (1) only GRP-27 reduced the first MS, (2) BN prolonged the IMI, (3) GRP-27 and BN increased the SR and (4) only BN reduced the size of the second meal. Contrary to our hypothesis, the i.v. administration of GRP-27 and BN affected the MS and IMI differently than did the i.p. administration. In conclusion, this pharmacological study suggests that the MS and IMI are regulated at different sites.