ABSTRACT
AIM: To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. METHODS: Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). RESULTS: Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. CONCLUSION: The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.
ABSTRACT
OBJECTIVE: To observe the effects of Astragalus polysaccharides (APS) on the BG, insulin and C-peptide in serum, ultrastructure and Fas expression of pancreatic beta-cells in diabetes mellitus (DM) rats. METHODS: Thirty DM rats induced by streptozotocin (STZ) were randomly divided into three groups: DM group, APS 200 mg/kg group, APS 400 mg/kg group, another 10 normal rats were taken as the control group. The drug was given by intraperitoneal for 6 weeks. The level of BG was determined by ONE TOUCH II machine. The levels of insulin and C-peptide in serum were measured by radioimmunoassay. The expression of Fas was observed by immunohistochemistry. Moreover, the TEM was used to observe the ultrastructure of pancreatic beta-cells. RESULTS: (1) DM rats showed significant increase in BG compared with control group (P < 0.05). APS could decrease the level of FG (P < 0.05). (2) DM rats showed significant decrease in insulin and C-peptide in serum compared with control group (P < 0.05). APS has no appearance effects on the levels of them (P > 0.05). (3) The expression of Fas of beta-cells was significantly increased in DM rats, which was significantly inhibited by APS treatment. (4) It showed degenerative changes of pancreatic beta-cells ultramicroscopic structure of the DM rats, while APS treatment could significantly improve the damage. CONCLUSION: APS exerts its therapeutic effects on DM, which maybe related to the significant decreasing of the Fas expression and inhibiting the apoptosis of beta-cells.
