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 c...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. B2 R 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 Ca MKⅡ failed to suppress BK-induced PGE2 production. CONCLUSION: The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2 R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, Ca MK, IP3 and MAPK.展开更多
基金Supported by Grants from the Shandong Provincial Natural Science Foundation,China,No.ZR2009CL047 and No.ZR2011HM043the Scientific Research Foundation for Returned Scholars(Ministry of Education of China,2011,43~(th))+1 种基金Shandong Province Higher Educational Science and Technology Program,No.J14LK15Excellent Teachers International Training Cooperation Program of Shandong Province(for Yang XY and Qu MH)
文摘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. B2 R 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 Ca MKⅡ failed to suppress BK-induced PGE2 production. CONCLUSION: The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2 R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, Ca MK, IP3 and MAPK.
