Journal of Neuroscience, Vol 14, 5570-5579, Copyright © 1994 by Society for Neuroscience
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
KF Shen and SM Crain
Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461.
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 Ca(2+)-dependent component of the
action potential (APD) in a major subset of DRG neurons that were
previously shown to have characteristic responsiveness to exogenous
opioids. These NGF-elicited excitatory modulating effects are blocked by
pretreatment of the DRG neurons with monoclonal antibodies to rodent NGF
receptors. NGF-induced APD prolongation is also prevented by the opioid
receptor antagonist naloxone and the specific kappa-opioid antagonist
nor-binaltorphimine (but not by specific mu- and delta- opioid
antagonists). The results suggest that NGF stimulates the release of
endogenous opioids (e.g., dynorphin) from DRG neurons and that prolongation
of 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 prolong the
APD in view of the remarkable sensitivity of these neurons to the
excitatory effects of extremely low (fM-nM) concentrations of exogenous
opioid agonists. NGF-induced APD prolongation is blocked by the same
cholera toxin A or B subunit treatments previously shown to block Gs
coupling and GM1 ganglioside regulation of excitatory opioid receptors,
respectively. These in vitro studies suggest that excitatory opioid
receptor-mediated functions may play a role in mediating some types of
rapid NGF-induced hyperalgesic and other physiologic effects on the nervous
system.
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