|Budget Amount *help
¥12,900,000 (Direct Cost : ¥12,900,000)
Fiscal Year 1999 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1998 : ¥7,900,000 (Direct Cost : ¥7,900,000)
Fiscal Year 1997 : ¥3,000,000 (Direct Cost : ¥3,000,000)
The results may be summarized as follows :
1. GLP-1 with a variety of amino acid sequences may be the most potent inhibitor of food intake in chicken, and central GLP-1 may interact with NPY.
2. The fragments of GLP-1 (7-16) and GLP-1 (7-26) did not show the suppressive effect on food intake. Furthermore, the extended fragments, GLP-1 (7-30) and GLP-1 (7-33), also had no effect on feeding behavior. It is concluded that C-terminal amino acids of GLP-1 (7-36) also have an important role for the bioactivity in the central nervous system with special reference to feeding behavior.
3. Intracerebroventricular administration of exendine (9-39), a specific GLP-1 receptor antagonist in mammals, at the level of 0.5, 1 and 2 μg did not alter food intake of chicks compared with then saline control. It is concluded that modification of amino acids of exendine (9-39) may be required to antagonize chicken GLP-1 receptor.
4. Intracerebroventricular administration of substituted GLP-1 (7-36) in which N-ter
minal histidine of mammalian GLP-1 (7-36) amide was replaced with tyrosine, inhibited food intake in the chick, although the effect of substituted GLP-1 (7-36) was 11 to 13 fold less than that of mammalian GLP-1 (7-36) amide. These results indicate that His7 is an important for efficacy, but not essential for its bioactivity.
5. Intracerebroventricular administration of GLP-1 (7-36) amide altered, in a dose-dependent fashion,-the behavioral postures of chicks and induced sleep-like behavior compared with the saline control. These results indicate that GLP-1 (7-36) amide in the central nervous system may be one of the factors to induce sleeping of the neonatal chick.
6. The intraperitoneal injection of non-selective opiate antagonist, naloxone, did not influence the effect of Intracerebroventricular administration of mammalian GLP-1 (7-36) on feeding behavior. It is suggested that the central effect of GLP-1 is not presumably mediated by the action of endogenous opioids.
7. Central administration of AII (0, 25, 50 and 100 ng) increased water intake for 30 min in a dose dependent manner under an ad lib drinking condition. Water intake was decreased by co-injection with GLP-1 (30ng) in both AII (100ng) treated and control groups. These results suggest that central GLP-1 may be the regulator of water intake in the neonate chick.
8. And, BALB/c mice were received the intraperitoneal injection of GLP-1, and the marked serum antibody response was induced for all mice. Further the conjugaton of the spleens from the immuned mice and mouse myeloma cells are in progress to obtain monoclonal antibodies specific for chicken GLP-1. Less