Neurokinin B potentiates ATP-activated currents in rat DRG neurons

This study aimed to explore whether NKB could modulate the responses mediated by ATP receptor (P2X purinoceptor). Whole-cell patch clamp and repatch experiments were performed on cultured rat DRG neurons. The majority of neurons examined were sensitive both to ATP and to NKB (77.1%, 54/70). NKB preapplied could potentiate ATP-activated currents (I-ATP) markedly; this effect was concentration-dependent and could be blocked by SR 142801, an NK3 receptor antagonist. Preapplication of 0.001, 0.01, 0.1 and 1.0 muM NKB increased ATP-activated currents by 55.1 +/- 18.8, 75.2 +/- 17.4, 84.1 +/- 18.8 and 81.0 +/- 21.7%, respectively. The concentration-response curves for ATP with and without preapplication of NKB show that: (1) preapplication of NKB shifted the curve upwards; (2) the maximal amplitude Of I-ATP with NKB preapplication increased by 78.5%, while the threshold value remained unchanged; (3) the EC50 values of the two curves were very close (44 vs. 42 muM). Intracellular dialysis of H-7 by using repatch clamp technique could block the potentiation of I-ATP by NKB. It suggests that this potentiating effect was caused by phosphorylation of ATP receptor, which resulted from the activation of G protein coupled NK3 receptor and consequential intracellular signal transduction cascade. (C) 2001 Published by Elsevier Science B.V.