Pharmacological characteristics of bombesin receptor mediating hypothermia in the central nervous system of rats.
Bombesin (BN) and structurally related peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), injected into the lateral ventricle produce multiple effects such as hypothermia, anorexia and hormone release. In this study, the pharmacological characteristics of BN receptors mediating hypothermia in the central nervous system (CNS) were investigated using free-moving male Wistar rats. Intracerebroventricular injections of BN, GRP and NMB produced hypothermia in a dose-dependent manner. The BN (0.3 microg)-induced effect showed a short latency and a 4-h duration with a potency increased by more than 100 times compared to the NMB-induced effect. Pretreatment with [D-Tyr(6)]BN(6-13)methylester, a GRP receptor antagonist, inhibited the BN (0.3 microg)- and NMB (7 microg)-induced hypothermia. On the other hand, BIM23127, an NMB receptor antagonist, did not influence the hypothermia. Of the protein kinase C (PKC) inhibitors, chelerythrine, Go6983, staurosporine and GF109203X, the first two partially blocked the BN-induced hypothermia. A PKC activator, phorbol-12,13-dibutyrate, decreased the rectal temperature. Genistein (a tyrosine kinase inhibitor), Y-27632 (a Rho kinase inhibitor) and PD98059 (a MAPK inhibitor) tended to suppress the BN-induced hypothermia, however, these were not significant. The inhibitory effect of a mixture of the three inhibitors, chelerythrine, genistein and Y-27632, on the BN-induced hypothermia was of a similar degree to that of chelerythrine alone. The BN receptor mediating the hypothermia seem to be the GRP subtype, and the effect involves activation of PKC.
Tsushima
Hiromi
H
Department of Cellular and Molecular Pharmacology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-ku, 467-8601, Nagoya, Japan. tsushima@med.nagoya-cu.ac.jp
Mori
Mayumi
M
Fujiwara
Nakako
N
Moriyama
Akihiko
A
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001839:Bombesin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide / Q000008:administration & dosage / Q000494:pharmacology; D007035:Hypothermia / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D015287:Neurokinin B / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C081358:bombesin (6-13), Tyr(6) methyl ester; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D011493:Protein Kinase C; D001839:Bombesin