Bradykinin-Induced Nuclear Factor of Activated T-Cells- Dependent Transcription in Rat Dorsal Root Ganglion Neurons

Bradykinin produced at sites of tissue injury and inflammation elicits acute pain and alters the sensitivity of nociceptive neu-rons to subsequent stimuli. We tested the hypothesis that bradykinin could elicit long-lasting changes in nociceptor func-tion by activating members of the nuclear factor of activated T-cells (NFAT) family of transcription factors. Bradykinin acti-vation of B2 receptors evoked concentration-dependent (EC50 6.0 0.3 nM) increases in intracellular Ca 2 concen-tration ([Ca2]i) in a proportion of dorsal root ganglion neurons in primary culture. These [Ca2] increases were sensitive to inhibition of phospholipase C (PLC) and depletion of Ca2 stores. In neurons expressing a green fluorescent protein (GFP)-NFAT4 fusion protein, a 2-min exposure to bradykini