gastrin-releasing-peptide and Anorexia

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.

Topics: Animals; Anorexia; Bombesin; Eating; Gastrin-Releasing Peptide; Lateral Ventricles; Male; Microinjections; Motor Activity; Rats; Rats, Wistar; Telencephalon

Bombesin (BN) and its mammalian counterpart gastrin-releasing peptide (GRP) act as neuroregulatory hormones and peripheral and central satiety-inducing agents. Previously, we demonstrated that irradiation induces an increase in the expression of BN/GRP in the innervation of the salivary glands in rats. We therefore carried out a study using radioimmunoassay (RIA) analysis and immunohistochemistry to examine whether saliva contains BN and whether irradiation affects the BN release to saliva in rats. Immunoreactivity for BN was detected not only in the innervation of the parenchyma but also in the duct cells and in the lumina of the ducts, suggesting entrance of BN into saliva. The RIA analysis confirmed that rat saliva contains a BN-like peptide. The observation shows that saliva contains this peptide but that there is no significant increase following the radiation schedule used. Nevertheless, the occurrence of an enhanced expression of BN in different peripheral tissues such as the salivary and laryngeal glands should be taken into consideration when discussing the clinically important problem of reduced food intake and anorexia in cancer patients.

Topics: Animals; Anorexia; Bombesin; Female; Gastrin-Releasing Peptide; Immunohistochemistry; Radioimmunoassay; Radiotherapy; Rats; Rats, Sprague-Dawley; Saliva; Salivary Glands; Satiation