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J Neurophysiol 79: 670-676, 1998;
0022-3077/98 $5.00
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The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 670-676
Copyright ©1998 The American Physiological Society

Inflammatory Mediators at Acidic pH Activate Capsaicin Receptors in Cultured Sensory Neurons From Newborn Rats

Ladislav Vyklický1, Helena Knotková-Urbancová1, Zdenka Vitásková1, VIKTORIE Vlachová1, Michaela Kress2, and Peter W. Reeh2

1 Institute of Physiology, AS CR, 14220 Prague 4, Czech Republic; 2 Institut für Physiologie und Experimentelle Pathophysiologie, D-91054 Erlangen, Germany

Vyklický, Ladislav, Helena Knotková-Urbancová, Zdenka Vitásková, Viktorie Vlachová, Michaela Kress, and Peter W. Reeh. Inflammatory mediators at acidic pH activate capsaicin receptors in cultured sensory neurons from newborn rats. J. Neurophysiol. 79: 670-676, 1998. Whole cell membrane currentsinduced by the inflammatory mediators, bradykinin, 5-hydroxytryptamine (5-HT) and prostaglandin E2, were investigated in capsaicin-sensitive dorsal root ganglion (DRG) neurons from newborn rats grown on a monolayer of hippocampal glia without nerve growth factor (NGF). When firmly attached to an underlying cell, the neurons survived >14 days without growing extensive processes. A majority of the small diameter neurons (~80%) exhibited sensitivity to capsaicin (3-6 µM) and this was enhanced in solution of low pH. In acidic extracellular solution (pH 6.1), the combination of bradykinin (10 µM), 5-HT (10 µM) and prostaglandin E2 (1 µM) induced an inward membrane current in all capsaicin-sensitive DRG neurons (n = 43). The current exceeded the sustained, low pH-induced membrane current by 205 ± 53 (SE) pA. The combination of acidic inflammatory mediators was ineffective in cells that were insensitive to capsaicin. In capsaicin-sensitive neurons, the inflammatory mediators when applied singly or in any combination of two, induced no membrane currents or small current at pH 7.3 and 6.1. Capsazepine (10 µM), the capsaicin antagonist, completely inhibited the facilitatory action of inflammatory mediator combination but not the sustained inward current induced by acidic extracellular solution (pH 6.1 or 5.5). It is suggested that the inflammatory mediators, bradykinin,5-HT, and prostaglandin E2 together act as endogenous mediators at capsaicin receptors to generate an inward current when the ion channel is protonized.




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