Potentiating mechanism of glutathione on bradykinin mediated contraction in isolated guinea pig ileum

Bradykinin (BK) is an endogenous nonapeptide of kinin system with multi-biological effects including vasodilation in cardiovascular system and contraction of smooth muscle. BK has a relative short half life of less than 1 minute because it can be destroyed by plasma kininases or angiotensin converting enzyme (ACE). Several compounds including thiol-containing compounds have been reported their ability in potentiating BK actions. In this study, the investigated potentiating mechanisms of glutathione (GSH) on BK mediated contraction were in isolated guinea pig ileum. The ileum was isolated from male Dunkin Hartley Guinea pigs (250 350 g). The results showed that GSH at the concentration of 20.21 micromolar elicited the maximum potentiation on BK-induced contraction. In addition, an increase in contractile responses did not correlate with an increase in concentration of GSH. GSH (20.21 micromolar) did not cause an immediate potentiating response to BK (3nM). However, exposure to GSH for 5 minutes incubation significantly potentiated contractile responses to BK by 39.5+_7.41% (P < 0.05). An increase in incubation time from 5 minutes to 30 minutes did not significantly enhance the ileal contraction in response to BK. Furthermore, the potentiation effects of GSH was not observed when cumulative addition of various contractants including acetycholine, histamine, BaCl[subscript 2] and serotonin were used instead of BK. In the presence of QSA (10[subscript-6]M), the potentiation effect of GSH increase significantly by 52.5+_4.83% (P < 0.05). The potentiation effects of GSH, however, did not increase in the presence of L-NAME or in the absence of Ca[subscript 2+] in Tyrode's solution. Moreover, thiol-containing compounds including N-acetycysteine, homocysteine, dithiothreitol and captopril (20.21 micromolar) significantly potentiated contractile responses to BK. In conclusion, the potentiating effects of GSH on BK-mediated ileal contraction appeared to be restrictive to time and concentration. In addition, the potentiating effects of GSH on ileal contraction was specific to BK. It is possible that the potentiation effects of GSH was attributed to receptor sensitization and other mechanism in addition to ACE inhibiton. The potentiating mechanisms of GSH was not found to be correlated with an alteration no pathway and intracellular Ca[subscript 2+] under the present conditions.