새로운 항궤양제(IY-80843과 IY-80845)의 기니픽 위점막세포 H2-수용체에 대한 결합반응연구

Study on the Binding of New Anti-ulcer Agent(IY-80843 and IY-80845) to Histamine H2-Receptor in Isolated Guinea Pig Gastric Glands

Receptor binding study was carried out as an in vitro assay to test the anti-ulcer effect for newly synthesized test compounds(IY-80843 and IY-80845) which were reported to have a strong anti-secretory effect in Shay-ligated rats. The histamine H2-receptor fraction was prepared from the membranes of the isolated gastric glands in guinea pigs and 3H-cimetidine was used as a radioligand. The binding of 3H-cimetidine to the membranes of the isolated gastric glands was found to be time dependent, saturable and confined to a single population of binding sites with KD value of 0.13 +/- 0.03mcM and BMAX value of 52.5 +/- 1.5pmol/mg. From the competition experiments, both IY-80843 and IY-80845 were shown to have a strong blocking effect against binding of 3H-cimetidine to the histamine H2receptor. The IC50, Ki, and Hill coefficient(nH) values for IY-80843 were 0.18 +/- 0.02mcM, 0.16 +/- 0.02mcM, and 0.97 +/- 0.15, respectively and those values for IY-80845 were 0.27 +/- 0.02mcM, 0.24 +/- 0.02mcM, and 0.82 +/- 0.13, respectively. The results demonstrated that the blocking effects of IY-80843 and IY-80845 were 7 and 5 times stronger than that of cimetidine, respectively. Therefore, the newly synthesized compounds, IY-80843 and IY-80845, appeared to be the highly potent competitive inhibitors of histamine on the H2-receptor.