title: Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mei-Hua Qu, Ting-Kun Zhao, Chun-Yan Fang, Shu-Mei Mao, Zhi-Qin Gao, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang 261053, Shandong Province, China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Qu
authors.affiliation: Mei-Hua Qu, Ting-Kun Zhao, Chun-Yan Fang, Shu-Mei Mao, Zhi-Qin Gao, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang 261053, Shandong Province, China.
authors.forename: Wan-Sheng
authors.initials: WS
authors.lastname: Ji
authors.affiliation: Mei-Hua Qu, Ting-Kun Zhao, Chun-Yan Fang, Shu-Mei Mao, Zhi-Qin Gao, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang 261053, Shandong Province, China.
authors.forename: Ting-Kun
authors.initials: TK
authors.lastname: Zhao
authors.affiliation: Mei-Hua Qu, Ting-Kun Zhao, Chun-Yan Fang, Shu-Mei Mao, Zhi-Qin Gao, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang 261053, Shandong Province, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Mei-Hua Qu, Ting-Kun Zhao, Chun-Yan Fang, Shu-Mei Mao, Zhi-Qin Gao, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang 261053, Shandong Province, China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Mao
authors.affiliation: Mei-Hua Qu, Ting-Kun Zhao, Chun-Yan Fang, Shu-Mei Mao, Zhi-Qin Gao, Key Lab of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang 261053, Shandong Province, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Gao
keywords: Brandykinin; Brandykinin receptor; Chloride secretion; Cyclooxygenase; Prostaglandin E; Ussing chamber