Brief treatment of sensory ganglion neurons with GM1 ganglioside enhances the efficacy of opioid excitatory effects on the action potential.
In previous studies, we showed that low (nM) concentrations of opioid prolong the action potential duration (APD) of many mouse dorsal root ganglion (DRG) neurons via Gs-linked excitatory opioid receptors, whereas micromolar opioid levels shorten the APD via Gi/Go-linked inhibitory receptors. In addition, cholera toxin-B subunit (CTX-B) selectively blocks opioid- but not forskolin-induced prolongation of the APD in DRG neurons. Since CTX-B binds with selective high affinity to GM1 ganglioside located on the cell surface, the results suggest that GM1 plays an essential role in regulating excitatory opioid receptor functions. This hypothesis was tested by treating DRG neurons in mouse DRG-cord explants with exogenous gangliosides and determining whether the efficacy of opioid agonists in prolonging the APD is enhanced. The threshold concentration of the opioids, dynorphin(1-13) and morphine required to prolong the APD in many DRG neurons was markedly decreased from nM to fM levels after bath exposure to 10 nM to 1 microM GM1 ganglioside for less than 5 min. In contrast, GM2 and GM3 gangliosides and asialo-GM1 ganglioside were ineffective, even when DRG neurons were exposed to high concentrations (1-10 microM) for periods greater than 1 h. Although GD1a, GD1b and GQ1b gangliosides appeared to be as effective as GM1 when tested at microM concentrations for 15 min, tests at lower concentrations, shorter periods, and/or at lower temperature (24 degrees vs 34 degrees C), showed that they were significantly less effective than GM1.(ABSTRACT TRUNCATED AT 250 WORDS)
Shen
K F
KF
Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461.
Crain
S M
SM
Ledeen
R W
RW
D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D005732:Gangliosides / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D011957:Receptors, Opioid / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D013268:Stimulation, Chemical
D000700:Analgesics; D005732:Gangliosides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D005677:G(M1) Ganglioside; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; D002772:Cholera Toxin