Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP.
Bombesin (BN)-like peptides injected peripherally or centrally suppress food intake in rats. The relationship between the central and peripheral actions of BN is unknown. However, experimental evidence supports a critical role for the caudal hindbrain in mediating the feeding effects of BN. To investigate this relationship further, we examined the ability of fourth ventricular infusion of a specific gastrin-releasing peptide (GRP) antagonist, [D-F5, Phe6, D-Ala11]BN-(6-13) methyl ester (BN-ME), to block suppression of glucose intake (0.5 kcal/ml) produced by intraperitoneal administration of GRP-(18-27) in 5-h food-deprived male Sprague-Dawley rats (n = 10). We found that fourth ventricular administration of 10, 32, and 100 ng BN-ME blocked the suppression of glucose intake produced by peripherally administered 10 nmol/kg GRP-(18-27). The most effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of GRP-(18-27) to inhibit glucose intake but had no effect on intake when given alone. These results demonstrate that the availability of caudal hindbrain GRP receptors is necessary for peripherally administered GRP-(18-27) to reduce food intake in rats.
Ladenheim
E E
EE
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Taylor
J E
JE
Coy
D H
DH
Moore
K A
KA
Moran
T H
TH
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D005508:Food Deprivation; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D012249:Rhombencephalon / Q000378:metabolism*; D012528:Satiety Response / Q000502:physiology
C091872:BIM 26226; D005755:Gastrins; D010446:Peptide Fragments; D010455:Peptides; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; C040794:neuromedin C; D001839:Bombesin