Histamine H-1 receptors mediate the anorectic action of the pancreatic hormone amylin

We investigated the role of histamine H-1 receptors in mediating the anorec tic effect of intraperitoneally injected amylin (5 and 20 mug/kg), the amyl in agonist salmon calcitonin (sCT; 10 mug/kg), leptin (1.3 mg/kg), and chol ecystokinin (CCK; 20 mug/kg). The experiments were performed with mice lack ing functional H-1 receptors (H(1)Rko) and wild-type (WT) controls. The mic e were also injected with the H-3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through p resynaptic H-3 receptors. The feeding-suppressive effect of thioperamide wa s abolished in H(1)Rko mice. The anorectic effects of amylin and sCT were s ignificantly reduced in 12-hfood-deprived H(1)Rko mice compared with WT mic e [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 mug/kg) 0.30 /- 0.06 g (P< 0.01); H(1)Rko-NaCl 0.45 +/- 0.05 g vs. H(1)Rko-amylin 0.40 /- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 <mu>g/kg) 0.14 +/- 0.10 g (P< 0.05); H(1)Rko-NaCl 0.44 +/- 0.08 g vs. H(1)Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H(1)Rko mice, w hereas CCK equally reduced feeding in WT and H(1)Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effec ts of peripheral amylin and sCT via histamine H-1 receptors. The same appli es to leptin but not to CCK. H(1)Rko mice showed significantly increased bo dy weight gain compared with WT mice, supporting the role of endogenous his tamine in the regulation of feeding and body weight.