Mechanisms of modulation of pregnanolone on glycinergic response in cultured spinal dorsal horn neurons of rat

Jiang, Peng; Yang, Chuan-Xiu; Wang, Yu Tian; Xu, Tian‐Le

doi:10.1016/j.neuroscience.2006.05.009

Cited by 39 publications

(28 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A previous study showed that another neurosteroid, pregnanolone (PGN) directly inhibited I Gly in a competitive manner [39]. We were interested to know whether E 2 and PGN share a common binding site on GlyRs.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Glycine Receptor in Rat Hippocampal and Spinal Cord Neurons as a Molecular Target for Rapid Actions of 17-β-Estradiol

et al. 2009

View full text Add to dashboard Cite

Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP) and spinal dorsal horn (SDH) neurons, 17-β-estradiol (E2) rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents (IGly). In outside-out membrane patches from HIP neurons devoid of nuclei, E2 similarly inhibited IGly, suggesting a non-genomic characteristic. Moreover, the E2 effect on IGly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i.e. ERα and ERβ) antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E2 only affected the IGly in cells expressing α2, α2β or α3β subunits, suggesting that either α2-containing or α3β-GlyRs mediate the E2 effect observed in neurons. Furthermore, E2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CA1 region, where abundant GlyR α2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level.

show abstract

Section: Resultsmentioning

confidence: 99%

“…All constructs were expressed in HEK293 cells as previously reported [39]. In brief, HEK293 cells were cultured at 37°C in a humidified atmosphere of 5% CO2 and 95% air.…”

Section: Methodsmentioning

confidence: 99%

Glycine Receptor in Rat Hippocampal and Spinal Cord Neurons as a Molecular Target for Rapid Actions of 17-β-Estradiol

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The SDH neurons from 15-d-old embryonic Sprague Dawley rats were isolated by a standard enzyme treatment protocol (Jiang et al, 2006). Briefly, SDH neurons were dissociated in Ca 2ϩ -free saline with sucrose (20 mM) and plated (1 ϫ 10 5 cell/ml) on poly-Dlysine (Sigma, St. Louis, MO)-coated cover glasses.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of Acid-Sensing Ion Channel ASIC1a in Spinal Dorsal Horn Neurons Contributes to Inflammatory Pain Hypersensitivity

Duan

Yu³

et al. 2007

J. Neurosci.

Self Cite

149

161

View full text Add to dashboard Cite

show abstract

“…On the other hand, some synthetic GABA-potentiating steroids augment glycine responses generated by recombinant glycine receptors (Lambert et al, 2001). Recent papers, however, reported significant antagonistic effects of 3α5βP on native and recombinant glycine receptors (Jiang et al, 2006;Weir et al, 2004). Also, sulfated steroids antagonize glycine receptors (Maksay et al, 2001;Wu et al, 1997), and pregnenolone potentiates glycine receptors in a subunit-specific manner (Maksay et al, 2001).…”

Section: C Actions Of Neurosteroids Not Involving Gaba a Receptorsmentioning

confidence: 99%

Mechanisms of neurosteroid interactions with GABAA receptors

Akk¹,

Covey²,

Evers³

et al. 2007

Pharmacology & Therapeutics

149

166

View full text Add to dashboard Cite

Neuroactive steroids have some of their most potent actions by augmenting the function of GABA A receptors. Endogenous steroid actions on GABA A receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABA A receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.

show abstract

Mechanisms of modulation of pregnanolone on glycinergic response in cultured spinal dorsal horn neurons of rat

Cited by 39 publications

References 54 publications

Glycine Receptor in Rat Hippocampal and Spinal Cord Neurons as a Molecular Target for Rapid Actions of 17-β-Estradiol

Glycine Receptor in Rat Hippocampal and Spinal Cord Neurons as a Molecular Target for Rapid Actions of 17-β-Estradiol

Upregulation of Acid-Sensing Ion Channel ASIC1a in Spinal Dorsal Horn Neurons Contributes to Inflammatory Pain Hypersensitivity

Mechanisms of neurosteroid interactions with GABAA receptors

Contact Info

Product

Resources

About