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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin

¹Departments of Medicine, Division of Hepatology, Gastroenterology, and Endocrinology, Charité-Universitätsmedizin Berlin, Campus Virchow, Berlin; ²Department of Medicine, Division of Psychosomatic Medicine and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany; ³Institute of Anatomy, Section of Electron Microscopy and Neuroanatomy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany; ⁴Department of Medicine, Division Gastroenterology and Endocrinology, Philipps-Universität Marburg, Germany; and ⁵Department of Medicine, Center for Ulcer Research and Education Digestive Diseases Research Center, Center for Neurovisceral Sciences, Digestive Diseases Division University of California Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California

Submitted 20 September 2005 ; accepted in final form 20 April 2006

The interaction between ghrelin and bombesin or amylin administered intraperitoneally on food intake and brain neuronal activity was assessed by Fos-like immunoreactivity (FLI) in nonfasted rats. Ghrelin (13 µg/kg ip) increased food intake compared with the vehicle group when measured at 30 min (g/kg: 3.66 ± 0.80 vs. 1.68 ± 0.42, P < 0.0087). Bombesin (8 µg/kg) injected intraperitoneally with ghrelin (13 µg/kg) blocked the orexigenic effect of ghrelin (1.18 ± 0.41 g/kg, P < 0.0002). Bombesin alone (4 and 8 µg/kg ip) exerted a dose-related nonsignificant reduction of food intake (g/kg: 1.08 ± 0.44, P > 0.45 and 0.55 ± 0.34, P > 0.16, respectively). By contrast, ghrelin-induced stimulation of food intake (g/kg: 3.96 ± 0.56 g/kg vs. vehicle 0.82 ± 0.59, P < 0.004) was not altered by amylin (1 and 5 µg/kg ip) (g/kg: 4.37 ± 1.12, P > 0.69, and 3.01 ± 0.78, respectively, P > 0.37). Ghrelin increased the number of FLI-positive neurons/section in the arcuate nucleus (ARC) compared with vehicle (median: 42 vs. 19, P < 0.008). Bombesin alone (4 and 8 µg/kg ip) did not induce FLI neurons in the paraventricular nucleus of the hypothalamus (PVN) and coadministered with ghrelin did not alter ghrelin-induced FLI in the ARC. However, bombesin (8 µg/kg) with ghrelin significantly increased neuronal activity in the PVN approximately threefold compared with vehicle and 1.5-fold compared with the ghrelin group. Bombesin (8 µg/kg) with ghrelin injected intraperitoneally induced Fos expression in 22.4 ± 0.8% of CRF-immunoreactive neurons in the PVN. These results suggest that peripheral bombesin, unlike amylin, inhibits peripheral ghrelin induced food intake and enhances activation of CRF neurons in the PVN.

c-fos; food intake

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