The H3 receptor is involved in cholecystokinin inhibition of food intake in rats.
We investigated the peripheral effects of an H3-receptor agonist and an H3-receptor antagonist (R)alpha-methylhistamine (Ralpha-MeHA) and thioperamide, respectively, on basal feeding and the CCK8-induced inhibition of food intake in rat. Intraperitoneal injection of thioperamide reduced food intake in a dose-dependent manner with maximal inhibition (35%, P<0.01 vs saline) at 3 mg/kg. (R)alpha-MeHA (0.3-3 mg/kg i.p.), an H3-receptor agonist alone had no effect on feeding but reversed the thioperamide-induced inhibition of food intake in a dose-dependent manner. The maximal feeding inhibitory dose of thioperamide (3 mg.kg i.p) increased by 40% and 22 % (P<0.01 vs saline) brain and stomach histamine contents, respectively. Histamine (0.3 - 6 mg/kg i.p.) and CCK-8 (3 - 30 microg/kg i.p) also inhibited food intake in a dose-dependent manner. Inhibition was 20% to 40% for histamine and 40% to 80% (P<0.01 vs saline) for CCK8. CCK-8 inhibition of feeding was increased by thioperamide and prevented by (R)alpha-MeHA in a dose-dependent way. In addition, CCK-8 did not reduce food intake if rats were pretreated with pyrilamine or ranitidine postsynaptic H1- and H2-receptor antagonists respectively. Our data suggest that the H3-receptor is involved in basal feeding. They also suggest that CCK satiety depends upon the release of histamine which acts on the H2- and H1-receptors, the final mediators of this effect.
Attoub
S
S
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 10, IFR2 Cellules Epithéliales Hĵpital Bichat, Paris, France.
Moizo
L
L
Sobhani
I
I
Laigneau
J P
JP
Lewin
M J
MJ
Bado
A
A
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005753:Gastric Mucosa / Q000378:metabolism; D006632:Histamine / Q000008:administration & dosage / Q000378:metabolism; D017442:Histamine Agonists / Q000008:administration & dosage*; D006633:Histamine Antagonists / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D008761:Methylhistamines / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011738:Pyrilamine / Q000008:administration & dosage; D011899:Ranitidine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D012844:Sincalide / Q000008:administration & dosage; D013270:Stomach / Q000187:drug effects
D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D006632:Histamine; D011899:Ranitidine; D002766:Cholecystokinin; D011738:Pyrilamine; C052075:thioperamide; D012844:Sincalide