. Effect of CCK-1 receptor blockade on ghrelin and PYY secretion in men. Am J Physiol Regul Integr Comp Physiol 292: R1391-R1399, 2007. First published November 30, 2006; doi:10.1152/ajpregu.00734.2006, peptide YY (PYY), and ghrelin have been proposed to act as satiety hormones. CCK and PYY are stimulated during meal intake by the presence of nutrients in the small intestine, especially fat, whereas ghrelin is inhibited by eating. The sequence of events (fat intake followed by fat hydrolysis and CCK release) suggests that this process is crucial for triggering the effects. The aim of this study was therefore to investigate whether CCK mediated the effect of intraduodenal (ID) fat on ghrelin secretion and PYY release via CCK-1 receptors. Thirty-six male volunteers were studied in three consecutive, randomized, double-blind, cross-over studies: 1) 12 subjects received an ID fat infusion with or without 120 mg orlistat, an irreversible inhibitor of gastrointestinal lipases, compared with vehicle; 2) 12 subjects received ID long-chain fatty acids (LCF), ID medium-chain fatty acids (MCF), or ID vehicle; and 3) 12 subjects received ID LCF with and without the CCK-1 receptor antagonist dexloxiglumide (Dexlox) or ID vehicle plus intravenous saline (placebo). ID infusions were given for 180 min. The effects of these treatments on ghrelin concentrations and PYY release were quantified. Plasma hormone concentrations were measured in regular intervals by specific RIA systems. We found the following results. 1) ID fat induced a significant inhibition in ghrelin levels (P Ͻ 0.01) and a significant increase in PYY concentrations (P Ͻ 0.004). Inhibition of fat hydrolysis by orlistat abolished both effects. 2) LCF significantly inhibited ghrelin levels (P Ͻ 0.02) and stimulated PYY release (P Ͻ 0.008), whereas MCF were ineffective compared with controls. 3) Dexlox administration abolished the effect of LCF on ghrelin and on PYY. ID fat or LCF significantly stimulated plasma CCK (P Ͻ 0.006 and P Ͻ 0.004) compared with saline. MCF did not stimulate plasma CCK release. In summary, fat hydrolysis is essential to induce effects on ghrelin and PYY through the generation of LCF, whereas MCF are ineffective. Furthermore, LCF stimulated plasma CCK release, suggesting that peripheral CCK is the mediator of these actions. The CCK-1 receptor antagonist Dexlox abolished the effect of ID LCF, on both ghrelin and PYY. Generation of LCF through hydrolysis of fat is a critical step for fat-induced inhibition of ghrelin and stimulation of PYY in humans; the signal is mediated via CCK release and CCK-1 receptors. peptide YY; cholecystokinin THE PROCESS OF FOOD INTAKE is coordinated by interactions between the enteric nervous system and gastrointestinal hormones (34, 36). Many gastrointestinal hormones are released from specialized endocrine cells into the circulation or serve as neurotransmitters that mediate signals from the enteric nervous system. These signals are transmitted from the gut to the brain and become integrated at various centers ...

This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration.

Objective: The aim of this study was to compare the effect on intragastric acidity over 24 h on days 1 and 3 following treatment with intravenous (i.v.) esomeprazole 40 mg (CAS for esomeprazole sodium: 161796-78-7) and pantoprazole 40 mg (CAS for pantoprazole sodium: 138786-67-1). Methods:In an open, randomised, twoway cross-over study, 36 healthy volunteers received esomeprazole (Nexium ® ) 40 mg or pantoprazole 40 mg, both administered once daily as an i.v. bolus injection for 3 consecutive days. Continuous 24-h pH recordings were made under standardised conditions at baseline and on days 1 and 3 of each treatment period. The primary variable was the percentage of time with intragastric pH > 4 during a 24-h period. Results: Time with intragastric pH > 4 was significantly greater with esomeprazole than with pantoprazole during the first 4 h (47.8 % vs. 18.9 %), as well as for the 24-h period of day 1 and day 3 (day 1: 38.8 % vs. 23.7 %; day 3: 55.0 % vs. 35.2 %, p<0.0001 for all times examined). Mean of median intragastric pH with esomeprazole was significantly higher than with pantoprazole during the 24-h period (day 1: 3.2 vs. 2.2, p<0.0001; day 3: 4.3 vs. 3.1, p<0.00001). Conclusion: Esomeprazole administered as a 40 mg i.v. bolus injection provided faster and more effective control of intragastric acidity than a 40 mg i.v. bolus injection of pantoprazole, and also maintained pH > 4 longer both during the first 4 h on day 1 and during the 24-h period of day 1 and day 3 of dosing.