NERVE GROWTH-FACTOR RAPIDLY PROLONGS THE ACTION-POTENTIAL OF MATURE SENSORY GANGLION NEURONS IN CULTURE, AND THIS EFFECT REQUIRES ACTIVATION OF GS-COUPLED EXCITATORY KAPPA-OPIOID RECEPTORS ON THESE CELLS

Application of low concentrations (pM-nM) of NGF to mouse dorsal root ganglion (DRG)-spinal cord explants in long-term organotypic cultures rapidly prolongs the duration of the Ca2+-dependent component of the a ction potential (APD) in a major subset of DRG neurons that were previ ously shown to have characteristic responsiveness to exogenous opioids . These NGF-elicited excitatory modulating effects are blocked by pret reatment of the DRG neurons with monoclonal antibodies to rodent NGF r eceptors. NGF-induced APD prolongation is also prevented by the opioid receptor antagonist naloxone and the specific kappa-opioid antagonist nor-binaltorphimmine (but not by specific mu- and delta-opioid antago nists). The results suggest that NGF stimulates the release of endogen ous opioids (e.g., dynorphin) from DRG neurons and that prolongation o f the APD occurs secondarily by activation of excitatory kappa-opioid receptor functions on these same or nearby cells. NGF-induced release of small quantities of opioids by DRG neurons would be expected to pro long the APD in view of the remarkable sensitivity of these neurons to the excitatory effects of extremely row (fM-nM) concentrations of exo genous opioid agonists. NGF-induced APD prolongation is blocked by the same cholera toxin A or B subunit treatments previously shown to bloc k Gs coupling and GM1 ganglioside regulation of excitatory opioid rece ptors, respectively. These in vitro studies suggest that excitatory op ioid receptor-mediated functions may play a role in mediating some typ es of rapid NGF-induced hyperalgesic and other physiologic effects on the nervous system.