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1 Institute of Veterinary Physiology, University of Zurich, 8057 Zurich, Switzerland; and 2 Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45267
We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 µg/kg), the amylin agonist salmon calcitonin (sCT; 10 µg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 µg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 ± 0.05 g vs. WT-amylin (5 µg/kg) 0.30 ± 0.06 g (P < 0.01); H1Rko-NaCl 0.45 ± 0.05 g vs. H1Rko-amylin 0.40 ± 0.04 g; WT-NaCl 0.40 ± 0.09 g vs. WT-sCT (10 µg/kg) 0.14 ± 0.10 g (P < 0.05); H1Rko-NaCl 0.44 ± 0.08 g vs. H1Rko-sCT 0.50 ± 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.
food intake; histamine H1 receptor knockout mice; thioperamide; salmon calcitonin; leptin; cholecystokinin
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