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J.G. Webb, R.W. Beuerman, A.K. Palkama, C.E. Crosson; Bradykinin Regulation of Trabecular Cell Function and Outflow Facility . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1139.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Bradykinin(BK) acts on trabecular meshwork (TM) cells to stimulate synthesis of PGE2 and other eicosanoids. The objective of the present study was to investigate interactions between BK and PGE2 signaling in TM cells, and to determine the consequences of BK actions on outflow facility. Methods: Signaling experiments were performed in primary cultures of bovine TM cells studied at passages 2 and 3. Determinations of outflow facility were conducted in preparations of isolated bovine or human anterior segments perfused at constant pressure of 11 mmHg. Results: Incubation of TM cells with BK produced a concentration-dependent (EC50=3.60±7.0 nM) elevation of intracellular free Ca2+. This effect was inhibited in cells pretreated with Hoe-140, a selective antagonist of B2 kinin receptors. Treatment of cells with PGE2, in comparison, had no effect on cellular Ca2+ but stimulated production of cAMP. Interestingly, incubation of cells with PGE2 in combination with BK(EC50=3.6±1.8 nM) resulted in a 3- to 5-fold enhancement of PGE2-induced cAMP formation, an effect that was again blocked by Hoe-140. BK treatment also produced a 2- to 3-fold enhancement of isoproterenol or cholera-toxin-stimulated cAMP but had no effect on forskolin-stimulated cAMP formation. The infusion of BK(100 nM) also produced significant increases (approximately 2-fold) in outflow facility in both bovine and human perfused anterior segments when compared with control perfusion. Conclusions: These results indicate that BK activates B2 kinin receptors in TM cells to amplify PGE2 signaling, possibly by enhancing the molecular interaction between activated Gs and the catalytic unit of the effector enzyme, adenylyl cyclase. Moreover, in anterior segments, BK significantly enhances aqueous outflow. The composite of these data raises the possibility that kinins produced within the eye may contribute to the regulation of trabecular cell function and outflow resistance in the TM. CR: None Support: Supported by NIH grants EY-09741, S-10-RR-13005 and RPB.
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