Effects of the P2-purinoceptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid on glutamatergic synaptic transmission in rat dorsal horn neurons of the spinal cord.
The effects of suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) on glutamatergic synaptic transmission were studied on dorsal horn lamina II neurons of rat spinal cord slice preparation and cultured dorsal horn neurons. Suramin at 100 microM significantly suppressed the amplitude of the evoked excitatory postsynaptic currents (EPSCs) by 33%, miniature EPSC (mEPSC) amplitude was decreased by 46% and the mEPSC frequency also decreased by 41%. PPADS at 50 microM had little effect on either the evoked EPSCs or mEPSCs. The lack of effect of PPADS on glutamatergic synaptic transmission suggests that the effect of suramin is less likely to be mediated by P2x receptors. When whole-cell (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) currents evoked by glutamate were examined, both suramin and PPADS showed no inhibition of peak amplitude. However, the onset of glutamate-evoked whole-cell currents became significantly slowed by suramin but not by PPADS. The suppression of synaptic transmission by suramin may be due, in part, to the slowed onset of glutamate-evoked AMPA currents. These results suggest that the analgesic effects of suramin shown in cancer patients and animal pain models may not be solely due to its antagonism to purinoceptors. PPADS is probably a more suitable antagonist for the study of synaptic P2x receptor function at excitatory synapses mediated by AMPA receptors.
Gu
J G
JG
Department of Physiology and Cellular Biophysics and the Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA. jgu@dental.ufl.edu
Bardoni
R
R
Magherini
P C
PC
MacDermott
A B
AB
D000818:Animals; D000831:Animals, Newborn; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005971:Glutamates / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013498:Suramin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D005971:Glutamates; D058919:Purinergic P2 Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid