Volume 120, Issue 2, Pages 361-368 (February 2001) Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit  Lukas P. Degen, Fuping Peng, Annette Collet, Livid Rossi, Silvia Ketterer, Yolanda Serrano, Finn Larsen, Christoph Beglinger, Pius Hildebrand  Gastroenterology  Volume 120, Issue 2, Pages 361-368 (February 2001) DOI: 10.1053/gast.2001.21174 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 1 Potency of BIM26226 as a GRP-receptor antagonist. (A) Effect of saline (control) or BIM26226 (5, 50, or 500 μg · kg−1 · h−1) on gallbladder contraction, induced by infusion of graded doses of human GRP (10, 30, or 90 pmol · kg−1 · h−1). Gallbladder volumes are expressed as percentages of the basal volume. Values are means ± SEM of 8 subjects. (B) Plasma CCK concentrations in the same studies. Results are expressed as means ± SEM of 8 subjects. In a dose-dependent fashion, BIM26226 reduced GRP-stimulated gallbladder contraction and inhibited CCK release. The highest dose (500 μg · kg−1 · h−1) completely inhibited GRP-stimulated functions. Gastroenterology 2001 120, 361-368DOI: (10.1053/gast.2001.21174) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 2 Effects of BIM26226 on gastric emptying and plasma CCK release. (A) Effect of BIM26226 on gastric emptying of a solid meal assessed by scintigraphy. Eight subjects received IV saline (control) or BIM26226 (500 μg · kg−1 · h−1) throughout the experiment. Results are expressed as the percentage of meal contents remaining in the stomach. Values are means ± SEM. BIM26226 significantly inhibited the lag phase as well as the emptying rate of the solid meal (P < 0.05) compared with saline (control). (B) Plasma CCK concentrations in the same studies. Results are expressed as means ± SEM of 8 subjects. With BIM26226, integrated plasma CCK release did not differ from control values. Gastroenterology 2001 120, 361-368DOI: (10.1053/gast.2001.21174) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 3 Effects of BIM26226 on gallbladder contraction and plasma CCK release. (A) Effect of BIM26226 on gallbladder contraction induced by duodenal perfusion of a liquid meal. Six subjects received IV saline (control) or BIM26226 (500 μg · kg−1 · h−1) throughout the experiment. Results are expressed as the percentage of basal (premeal) volumes. Values are means ± SEM. BIM26226 significantly (P > 0.05) reduced gallbladder contraction compared with saline (control). (B) Effect of BIM26226 on plasma CCK concentrations during the same studies. Results are expressed as means ± SEM of 6 subjects. Plasma CCK levels, with and without BIM26226, did not significantly differ, indicating that the effect of BIM26226 on gallbladder contraction was not mediated by circulating CCK. Gastroenterology 2001 120, 361-368DOI: (10.1053/gast.2001.21174) Copyright © 2001 American Gastroenterological Association Terms and Conditions