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Norepinephrine-induced calcium mobilization in C6 glioma cells
Jian-Zhong Han1, Wen Lin, Shu-Jie Lou
1Neuroscience Research Institute and Department of Neurobiology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Aim:
To investigate the mechanism underlying the norepinephrine-induced elevation in intracellular calcium concentration ([Ca2+]i) in C6 glioma cells.
Methods:
Measurement of [Ca2+]i was carried out using the dual-wavelength fluorescence method with fura-2 as the indicator.
Results:
Norepinephrine was found to induce concentration-dependent increases in [Ca2+ ]i through alpha1-adrenoreceptors. The [Ca2+]i elevations were extracellular-calcium independent and not influenced by the treatment of pertussis toxin. Pretreatments with either U73122 or thapsigargin abolished the subsequent cellular calcium responses to norepinephrine. Preincubation with phorbol 12-myristate 13-acetate (PMA) significantly reduce d the [Ca2+]i elevations, while protein kinase C inhibitors Ro31-8220 or GF-109203X completely blocked the inhibitory action of PMA. However, drugs either activating or inhibiting the function of protein kinase A had no effect on the [Ca2+]i elevations.
Conclusion:
Norepinephrine induces calcium mobilization from internal stores by activation of phospholipase C in C6 cells. The [Ca2+]i elevation is negatively regulated by the activation of protein kinase C.