Mechanisms underlying anorexia after microinjection of bombesin into the lateral cerebroventricle.
Intracerebroventricular (i.c.v.) injections of bombesin (BN) and gastrin-releasing peptide (GRP) dose-dependently decreased food intake in male Wistar rats fasted for 17 h. Neuromedin B (NMB) did not show any effect on food intake. After BN administration, locomotor activity did not significantly change, compared with a vehicle-injected group. The anorexia induced by BN (0.3 microg) was perfectly inhibited by pretreatment with a GRP-receptor antagonist, [D-Tyr(6)]BN(6-13) methyl ester (10 microg), an NO synthase inhibitor, L-nitro-arginine (30 microg), and a PKG inhibitor, H-9 (2 microg). The cGMP concentration in the hypothalamus increased 1 h after administration when compared with the vehicle-injected group. On the other hand, an NMB-receptor antagonist, BIM23127 (10 microg), and the protein kinase (PK) C inhibitors, chelerythrine (2 microg) and Go6983 (2 microg), inhibited only the late phase of the anorexia. A PKC activator, phorbol 12, 13-dibutyrate (3 microg), injected into the ventricle decreased food intake. These findings suggest that BN suppresses food intake mainly mediated through the GRP receptor and NO-cGMP-PKG pathway, and NMB receptor and PKC is partly involved in the late phase of the anorexia.
Tsushima
Hiromi
H
Department of Cellular and Molecular Pharmacology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan. tsushima@med.nagoya-cu.ac.jp
Mori
Mayumi
M
D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001839:Bombesin / Q000008:administration & dosage*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D019886:Gastrin-Releasing Peptide / Q000008:administration & dosage; D020547:Lateral Ventricles / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections / Q000379:methods*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013687:Telencephalon / Q000187:drug effects* / Q000502:physiology
D019886:Gastrin-Releasing Peptide; D001839:Bombesin