INFLAMMATORY MEDIATORS AT ACIDIC PH ACTIVATE CAPSAICIN RECEPTORS IN CULTURED SENSORY NEURONS FROM NEWBORN RATS

Whole cell membrane currents induced by the inflammatory mediators, br adykinin, 5-hydroxytryptamine (5-HT) and prostaglandin E-2, were inves tigated in capsaicin-sensitive dorsal root ganglion (DRG) neurons from newborn rats grown on a monolayer of hippocampal glia without nerve g rowth factor (NGF). When firmly attached to an underlying cell, the ne urons survived >14 days without growing extensive processes. A majorit y of the small diameter neurons (similar to 80%) exhibited sensitivity to capsaicin (3-6 mu M), and this was enhanced In solution of low pH. In acidic extracellular solution (pH 6.1), the combination of bradyki nin (10 mu M), 5-HT (10 mu M) and prostaglandin E-2 (1 mu M) induced a n inward membrane current in all capsacin-sensitive DRG neurons (n = 4 3). The current exceeded the sustained, low pH-induced membrane curren t by 205 +/- 53 (SE) pA. The combination of acidic inflammatory mediat ors was ineffective in cells that were insensitive to capsaicin. In ca psaicin-sensitive neurons, the inflammatory mediators when applied sin gly or in any combination of two, induced no membrane currents or smal l current at pH 7.3 and 6.1. Capsazepine (10 mu M), the capsaicin anta gonist, completely inhibited the facilitatory action of inflammatory m ediator combination but not the sustained inward current induced by ac idic extracellular solution (pH 6.1 or 5.5). It is suggested that the inflammatory mediators, bradykinin, 5-HT, and prostaglandin E-2 togeth er act as endogenous mediators at capsaicin receptors to generate an i nward current when the ion channel is protonized.