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 microM 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 EC(50) values of the two curves were very close (44 vs. 42 microM). 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.
Wang
M J
MJ
Research Center of Experimental Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Xiong
S H
SH
Li
Z W
ZW
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015287:Neurokinin B / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
D015287:Neurokinin B; D000255:Adenosine Triphosphate