Distinct roles of CysLT1 and CysLT2 receptors in oxygen glucose deprivation-induced PC12 cell death.

Cysteinyl leukotrienes are involved in ischemic brain injury, and their receptors (CysLT1 and CysLT2) have been cloned. To clarify which subtype mediates the ischemic neuronal injury, we performed permanent transfection to increase CysLT1 and CysLT2 receptor expressions in PC12 cells. Oxygen glucose deprivation (OGD)-induced cell death was detected by Hoechst 33258 and propidium iodide fluorescent staining as well as by flow cytometry. OGD induced late phase apoptosis mainly and necrosis minimally. Over-expression of CysLT1 receptor decreased and over-expression of CysLT2 receptor increased OGD-induced cell death. An agonist LTD4 (10−7M) also induced apoptosis, especially in CysLT2 receptor over-expressing cells. A selective CysLT1 receptor antagonist montelukast did not affect OGD-induced apoptosis; while non-selective CysLT receptor antagonist Bay u9773 inhibited OGD-induced apoptosis, especially in CysLT2 receptor over-expressing cells. Thus, CysLT1 and CysLT2 receptors play distinct roles in OGD-induced PC12 cell death; CysLT1 attenuates while CysLT2 facilitates the cell death.