title: 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.
abstract: 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.
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461.
authors.forename: K F
authors.initials: KF
authors.lastname: Shen
authors.forename: S M
authors.initials: SM
authors.lastname: Crain
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence; D002772:Cholera Toxin / Q000145:classification / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000494:pharmacology; D017950:Ganglia, Sensory / Q000166:cytology / Q000502:physiology*; D026121:Indole Alkaloids; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011930:Reaction Time / Q000187:drug effects; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000502:physiology*
chemical_list: D002227:Carbazoles; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D017473:Receptors, Opioid, kappa; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; C049985:staurosporine aglycone; D011493:Protein Kinase C