|Budget Amount *help
¥8,200,000 (Direct Cost : ¥8,200,000)
Fiscal Year 1999 : ¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥5,000,000 (Direct Cost : ¥5,000,000)
In humans, CCK has been known to stimulate pancreatic enzyme secretion via CCK-A receptors. Nevertheless, it was recently reported that gene expression of CCK-A receptor in the human pancreas could not be detected by Northen blot analysis. In the present study, we examined the mechanism of regulation of human pancreas by CCK and compared with those in mice and rats.
Any dose of CCK could not stimulate amylase release from the human pancreatic dispersed acini, whereas GRP and acetylsholine did. The amylase release stimulated by acetylcholein and GRP were inhibited by atropine and a GRP antagonist, respectively. CCK-A receptor gene expression was not detected by Northern blot analysis but CCK-B receptor gene expression was detected in the human pancreas. Autoradiography using aィイD1125ィエD1-CCK-8 revealed positive binding sites in the human pancreas and these bindings were replaced by a CCK-B receptor antagonist but not by a CCK-A receptor antagonist. 1ィイD1125ィエD1-CCK-8 also bound human duo
denum and was replaced by CCK-A receptor antagonist. Therefore, we confirmed that CCK-B receptors, not A receptors, were rich in human pancreas and that CCK did not stimulate amylase release from the acinar cells, directly.
In rats, vagal afferent nerves in the stomach was responsible for CCK and the excitation was blocked by CCK-A receptor antagonist, not by B receptor antagonist. Taken together, it is interpreted that CCK stimulated human pancreas via vagal afferent nerve and passing through the vagal complex in the brain (vago-vagal reflex).
The bile and pancreatic juice secretion were examined in CCD-B receptor gene knockout mice. The lack of CCK-B receptor did not modify these secretions, or pancreatic growth. Thus, CCK-B receptor is not mandatory for the bile and pancreatic secretion or other regulation may compensate CCK-B receptor function. The CCK-A receptor gene knockout mice have been generated. They shows normal growth and are fertile. The bile and pancreatic juice secretion were not stimulated by CCK but were responsible for other stimulants such as GRP and acetylcholine. The pancreatic wet weight was not different among three genotypes. In rats, CCK-A receptor gene expression has been known to appear after birth. We reported this gene expression was correlated with demthylation. Less