A New Intestinal Motility Agonist GK-1806, Its Function On The Intestine And Target Detection

Polypore D-32, which was growing on the eucalyptus, was discovered by a farmer in Liaoning province. And it has amazing effect on gastrointestinal dyskinesis,abdominal distention,dyspepsia,chronic constipation and etc. The international research on the polypore shows that it is nonpoisonous,edible,sweet and has important function on the regulation of metabolism,improve health,disease resistance,regulation of human's function. The ehuricoic acid in its fruiting body can be used for synthesis of steroid drug, which is the main drug of endocrine disease,impotence and some diseases of department of obstetrics & gynecology, it could be used for the adjunctive drug of mammary cancer,carcinoma of prostate and other malignant tumor. But its ingredient, which effect on the gastrointestinal tract, has never been reported including action mechanism and physicochemistry character. GK-1806 is a kind of intestinal agonist extracted from the polypore D-32. It is diffluent in water and remain stable in pH 0¹4. In this experiment, we utilize the ileal rabbit preparations in vitro as the organ of target, and then add different doses of GK-1806 and its control drug erythrocin to find out their dose-effect relationship. We also add NK3 special antagonist H-2788 to find out its target of motility, then ensure the effect of GK-1806 and its target, compare to erythrocin's effect. Maybe a new kind of model for intestinal motility drug screening could be established. Method: Add different doses of GK-1806 to the ileal rabbit preparations in vitro, and then observe its effect. As the same method observe erythrocin's effect. Add certain dose of NK3 special antagonist H-2788 to the ileal rabbit preparations in vitro, and then observe its effect. Add the certain dose of NK3 special antagonist H-2788 and different doses of GK-1806 to the ileal rabbit preparations in vitro together, and then observe their collective effect. Add the certain dose of NK3 special antagonist H-2788 and different doses of erythrocin to the ileal rabbit preparations in vitro together, and then observe their collective effect. At the same time, we observe contraction and wave in the computer of the ileal rabbit preparations in vitro going along above steps. Results: (1) Adding different doses of GK-1806 to the ileal rabbit preparations in vitro, we find out that as the dose increasing the effect increases gradually. Its dose-effect curve is the typical S shape. And its maximal effect value is 3.5 times of basical effect value. The ileal rabbit preparations in vitro never have spasm. (2) As to erythrocin, it also has an increasing effect following the dose increasing. Its dose-effect curve is also typical S shape. And its maximal effect value is 3 times of basical effect value. But when the contraction achieves the maximal effect, the ileal rabbit preparations in vitro have spasm. (3) The NK₃ special antagonist H-2788 has little effect on the ileal rabbit preparations in vitro. (4) Adding different doses of GK-1806 to the ileal rabbit preparations in vitro together with the certain dose of the NK₃ special antagonist H-2788, we can find out that the contraction effect was inhibited strongly. (5) Adding different doses of erythrocin to the ileal rabbit preparations in vitro together with the certain dose of the NK3 special antagonist H-2788, we can find out that the contraction effect was the same as using eryhtrocin alone. Conclusion: (1) The contractile effect of the ileal rabbit preparations can be promoted potently by GK-1806 potently. Its mechanism may bereact with the NK₃ receptor, and then cause the contractile effect of the ileal rabbit preparations through the enteric nervous system. (2) The NK₃ special antagonist H-2788 has little effect on the ileal rabbit preparations in vitro, which shows that the NK₃ receptor has little reaction at the basical contraction. (3) We can build up a new experiment model of new drug screening, which has high efficiency and high dose through this experiment that GK-1806's function on the ileal rabbit preparat...