INVESTIGATION ON PHYSIOLOGICAL ROLE OF BOMBESIN-LIKE PEPTIDE RECEPTOR SYSTEM IN BRAIN

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In this study, we aimed to clarify the physiological role of bombesin-like peptide receptors in mammalian brain. Previous studies showed an involvement of the system in various biological aspects, however, individual role of each bombesin-like peptide receptor in the aspects remains elusive. We generated knockout mice of three mammalian bombesin-like peptide receptors which are gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMBR) and bombesin receptor subtype 3 (BRS3). Behavioral analyses of the knockout mice revealed that GRPR knockout mice showed increased social responses and social investigatory behaviors. Since treatment of tranquilizer did not change the responses in GRPR knockout, increased social activities in GRPR knockout mice was unlikely caused by altered anxiety. Rather, the behavior of the knockout mice was thought to be a consequence of altered cognition of odors. GRPR knockout mice preferred the odor of other mice to their own, in contrast to wild type mice. In BRS3 knockout mice, we found mild obesity with high blood pressure. Behavioral examination of BRS3 knockout mice revealed hyperresponsiveness to palatable and aversive taste stimuli. In addition, BRS3 knockout mice had altered responsiveness to novel and social environment. Isolation rearing caused increased gain of body weight and food consumption in BRS3 knockout mice. These results suggest that the bombesin-like peptide receptor system is an important player in higher brain function. Besides the behavioral examination, we also tried to isolate a unknown endogenous ligand for BRS3, however, we did not identify the ligand in the term of this study.