Antagonistic targeting of the histamine H-3 receptor decreases caloric intake in higher mammalian species

Malmlof K, Hastrup S, Wulff BS, Hansen BC, Peschke B, Jeppesen CB, Hohlweg R, Rimvall K

doi:10.1016/j.bcp.2007.01.034

Research article - Peer-reviewed, 2007

Antagonistic targeting of the histamine H-3 receptor decreases caloric intake in higher mammalian species

Malmlof K, Hastrup S, Wulff BS, Hansen BC, Peschke B, Jeppesen CB, Hohlweg R, Rimvall K
Malmlöf, Kjell (ed.)

Abstract

The main purpose of this study was to examine the effects of a selective histamine H-3 receptor antagonist, NNC 38-1202, on caloric intake in pigs and in rhesus monkeys. The compound was given intragastrically (5 or 15 mg/kg), to normal pigs (n = 7) and subcutaneously (1 or 0.1 mg/kg) to obese rhesus monkeys (n = 9). The energy intake recorded following administration of vehicle to the same animals served as control for the effect of the compound. In addition, rhesus monkey and pig histamine H-3 receptors were cloned from hypothalamic tissues and expressed in mammalian cell lines. The in vitro antagonist potencies of NNC 38-1202 at the H-3 receptors were determined using a functional GTP gamma S binding assay. Porcine and human H-3 receptors were found to have 93.3% identity at the amino acid level and the close homology between the monkey and human H-3 receptors (98.4% identity) was confirmed. The antagonist potencies of NNC 38-1202 at the porcine, monkey and human histamine H-3 receptors were high as evidenced by K-i-values being clearly below 20 nM, whereas the K-i-value on the rat H-3 receptor was significantly higher (56 +/- 6.0 nM). NNC 38-1202, given to pigs in a dose of 15 mg/kg, produced a significant (p < 0.05) reduction (55%) of calorie intake compared with vehicle alone, (132.6 +/- 10.0 kca/kg day versus 59.7 +/- 10.2 kca/kg day). In rhesus monkeys administration of 0.1 and 1 mg/kg decreased (p < 0.05) average calorie intakes by 40 and 75%, respectively. In conclusion, the present study demonstrates that antagonistic targeting of the histamine H-3 receptor decreases caloric intake in higher mammalian species. (c) 2007 Elsevier Inc. All rights reserved

Published in

Biochemical Pharmacology
2007, Volume: 73, number: 8, pages: 1237-1242
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

SLU Authors

UKÄ Subject classification

Animal and Dairy Science
Veterinary Science

Publication Identifiers

DOI: https://doi.org/10.1016/j.bcp.2007.01.034

Permanent link to this page (URI)

https://res.slu.se/id/publ/16791