title: Effects of prostaglandin D2 on tetrodotoxin-resistant Na+ currents in DRG neurons of adult rat.
abstract: Tetrodotoxin-resistant (TTX-R) Na(+) channels play a key role in the generation of action potentials in nociceptive dorsal root ganglion (DRG) neurons and are an important target for the proinflammatory mediator prostaglandin E(2), which augments these currents. Prostaglandin D(2) (PGD(2)) is released in the tissue together with prostaglandin E(2), and it was reported to be antiinflammatory, but its effect on primary afferent neurons is unclear. In the present study we localised G(s)-protein-coupled DP1 and G(i)-protein-coupled DP2 receptors in DRG neurons, and we assessed the effect of PGD(2) on TTX-R Na(+) currents in patch-clamp recordings from small- to medium-sized cultured DRG neurons from adult rats. DP1 and DP2 receptor-like immunoreactivity was localised in the vast majority of DRG neurons. In all neurons, PGD(2) shifted conductance to more hyperpolarised potentials, depending on an action at Na(v)1.9 channels. In about one third of the neurons, PGD(2) additionally influenced Na(v)1.8 channels by facilitating conductance and by increasing maximal current amplitudes. Selective DP1 receptor activation increased the amplitude of TTX-R Na(+) currents of most neurons, but this effect was counteracted by DP2 receptor activation, which by itself had no effect. In the current-clamp mode, PGD(2) lowered the threshold for elicitation of an action potential and increased the number of action potentials per stimulus, an effect mainly depending on DP1 receptor activation. Thus, the net effect of PGD(2) on DRG neurons is pronociceptive, although the magnitude of the TTX-R Na(+) currents depends on the balance of DP1 and DP2 receptor activation.
authors.affiliation: Department of Physiology I, Neurophysiology, University Hospital of Jena, Jena, Germany Department of Anatomy II, University Hospital of Jena, Jena, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ebersberger
authors.forename: Gabriel
authors.initials: G
authors.lastname: Natura
authors.forename: Annett
authors.initials: A
authors.lastname: Eitner
authors.forename: Karl-Jürgen
authors.initials: KJ
authors.lastname: Halbhuber
authors.forename: Reinhard
authors.initials: R
authors.lastname: Rost
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism; D006827:Hydantoins / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: C533609:CAY 10471; D002227:Carbazoles; D006827:Hydantoins; D010975:Platelet Aggregation Inhibitors; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D026941:Sodium Channel Blockers; D013449:Sulfonamides; C058848:BW A868C; D013779:Tetrodotoxin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor