Does the histaminergic system mediate bombesin/GRP-induced suppression of food intake?
Bombesin (BN) and its mammalian homologue, gastrin-releasing peptide (GRP), are potent satiety agents and have been implicated in the physiological regulation of food intake. The mechanism(s) of action of this effect remains unclear. There is a functional and anatomic overlap between histamine and BN in relationship to feeding, which led us to hypothesize that BN may mediate its satiety effects through activation of the histaminergic system. To assess this contention, we examined the effects of R-alpha-methylhistamine (alpha-MH) and Imetit, selective H3-receptor agonists that inhibit the release and synthesis of histamine, on BN- or cholecystokinin (CCK)-induced satiety. In this report we present the first evidence for the role of histamine H3 receptors in the mediation of BN-elicited satiety. During the first hour of the 4-h daily feeding session, BN reduced food intake by > 50% relative to the control condition; this suppression was blocked by prior treatment with the H3-receptor agonist, alpha-MH. This blockade of BN-induced satiety was dose related and selective to BN as alpha-MH failed to attenuate sulfated CCK-8-induced satiety. When alpha-MH was administered alone, it failed to significantly affect food intake. The specificity of this effect was further supported by the demonstration that another H3 agonist, Imetit, was also able to block the feeding-suppressant effects of BN. Furthermore, thioperamide, an H3-receptor antagonist, blocked these effects of Imetit.(ABSTRACT TRUNCATED AT 250 WORDS)
Merali
Z
Z
School of Psychology, University of Ottawa, Ontario, Canada.
Banks
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001839:Bombesin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D019886:Gastrin-Releasing Peptide; D006632:Histamine / Q000502:physiology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012527:Satiation / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D010455:Peptides; D010880:Piperidines; C077430:imetit; C069357:alpha-methylhistamine; D019886:Gastrin-Releasing Peptide; D006632:Histamine; D013890:Thiourea; C052075:thioperamide; D012844:Sincalide; D001839:Bombesin