PLC and PKC signaling plays a role in basal BDNF secretion by ASM cells. Nonasthmatic and asthmatic ASM cells were treated, under serum-free conditions, with 5 μM U73122 (PLCγ inhibitor) or 10 ng/ml BIS (bisindolylmaleimide, a PKC inhibitor). Two hours later, cells were either exposed to medium or to 20 ng/ml TNF-α for 48 h, before cell supernatants were collected for quantifying BDNF secretion by ELISA. Inhibition of PLC or PKC signals attenuated BDNF secretion substantially, in both nonasthmatic and asthmatic ASM cells. In the presence of these inhibitors, TNF-α did not restore BDNF secretion in either of the cell types; n = 4 patients. *Significant difference from No Treatment-No TNF-α control, P < 0.05. #Significant difference between Nonasthmatic and Asthmatic cells, P < 0.05. $Significant difference between No Drug and Inhibitor systems, P < 0.05.