Nicotinic Acetylcholine Receptors Containing Subunits α3 and α5 in Rat Nociceptive Dorsal Root Ganglion Neurons

Spies, Markus; Lips, Katrin Susanne; Kurzen, Hjelmar; Kummer, Wolfgang; Haberberger, Rainer Viktor

doi:10.1385/jmn:30:1:55

Cited by 17 publications

(13 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in nAChR subunit expression and nicotine-evoked current primarily affected the peptidergic, GFRα3-positive DRG neuron subpopulation, which is consistent with findings of Flores and colleagues [14], who showed using in situ hybridization that α3 and β4 are co-expressed in medium-diameter neurons. This observation is also consistent with Spies et al [34] who reported small- to medium-sized neurons express the α3 nAChR subunit. In addition, since ~95% of GFRα3 neurons are TRPV1-positive, the overlap in GFRα3/nAChRα3 labeling is consistent with work of Dussor et al [12], who showed overlap of TRPV1 and nAChRα3 mRNAs, and studies of Roberts et al, and Rau et al, who used patch clamp analysis of isolated neurons to show functional overlap of nAChR and TRPV1 activity [15,16].…”

Section: Discussionsupporting

confidence: 93%

Artemin Growth Factor Increases Nicotinic Cholinergic Receptor Subunit Expression and Activity in Nociceptive Sensory Neurons

et al. 2014

View full text Add to dashboard Cite

BackgroundArtemin (Artn), a member of the glial cell line-derived growth factor (GDNF) family, supports the development and function of a subpopulation of peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is elevated in inflamed tissue and its injection in skin causes transient thermal hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute to Artn-induced sensitivity. Here we have used gene expression, immunolabeling, patch clamp electrophysiology and behavioral testing assays to investigate the link between Artn, nicotinic subunit expression and thermal hypersensitivity.ResultsReverse transcriptase-PCR validation showed increased levels of mRNAs encoding the nAChR subunits α3 (13.3-fold), β3 (4-fold) and β4 (7.7-fold) in trigeminal ganglia and α3 (4-fold) and β4 (2.8-fold) in dorsal root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased immunoreactivity for nAChRα3 and exhibited increased overlap in labeling with GFRα3-positive neurons. Patch clamp analysis of back-labeled cutaneous afferents showed that while the majority of nicotine-evoked currents in DRG neurons had biophysical and pharmacological properties of α7-subunit containing nAChRs, the Artn-induced increase in α3 and β4 subunits resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or hexamethonium. Complete Freund’s adjuvant (CFA) inflammation of paw skin, which causes an increase in Artn in the skin, also increased the level of nAChR mRNAs in DRG. Finally, the increase in nAChRs transcription was not dependent on the Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated in ganglia of TRPV1/TRPA1 double knockout mice.ConclusionsThese findings suggest that Artn regulates the expression and composition of nAChRs in GFRα3 nociceptors and that these changes contribute to the thermal hypersensitivity that develops in response to Artn injection and perhaps to inflammation.

show abstract

Section: Discussionsupporting

confidence: 93%

Artemin Growth Factor Increases Nicotinic Cholinergic Receptor Subunit Expression and Activity in Nociceptive Sensory Neurons

et al. 2014

View full text Add to dashboard Cite

show abstract

“…α7 nAChRs may be restricted to C afferents, whereas heteromeric nAChRs are expressed by both C and Aδ afferents (Rau et al, 2005). Dorsal root ganglia (DRG) express a majority of α3β4* and α6β4* and a minority of α3/α6β2* nAChRs (Hone, Meyer, McIntyre, & McIntosh, 2011), and functional studies indicate that around 50% of nociceptive neurons in these ganglia express α3/α6β2-sensitive nAChRs (Spies, Lips, Kurzen, Kummer, & Haberberger, 2006).…”

Section: Nociceptorsmentioning

confidence: 99%

Nicotinic Regulation of Energy Homeostasis

Zoli

Picciotto

2012

Nicotine & Tobacco Research

View full text Add to dashboard Cite

Introduction: The ability of nicotine, the primary psychoactive substance in tobacco smoke, to regulate appetite and body weight is one of the factors cited by smokers that prevents them from quitting and is the primary reason for smoking initiation in teenage girls. The regulation of feeding and metabolism by nicotine is complex, and recent studies have begun to identify nicotinic acetylcholine receptor (nAChR) subtypes and circuits or cell types involved in this regulation.

show abstract

“…Expression sites of α9 and α10 nAChR subunits further include the nasal epithelium and the pars tuberalis of the pituitary gland [16, 18], human and rat urothelium [78, 79], human and rat placenta [80-83], rat heart [84] and dorsal root ganglia [85-87]. Furthermore, α9 (α10 not investigated) is expressed in retina [88], sperm [89] and olfactory bulb [90], whereas α10 is expressed in arteries [91, 92] and rat sympathetic ganglia [93].…”

Section: Expression Pattern Of α9 and α10 Nachr Subunitsmentioning

confidence: 99%

Alpha9 nicotinic acetylcholine receptors and the treatment of pain

McIntosh

Absalom

Chebib

et al. 2009

Biochemical Pharmacology

137

135

View full text Add to dashboard Cite

Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.

show abstract

Nicotinic Acetylcholine Receptors Containing Subunits α3 and α5 in Rat Nociceptive Dorsal Root Ganglion Neurons

Cited by 17 publications

References 5 publications

Artemin Growth Factor Increases Nicotinic Cholinergic Receptor Subunit Expression and Activity in Nociceptive Sensory Neurons

Artemin Growth Factor Increases Nicotinic Cholinergic Receptor Subunit Expression and Activity in Nociceptive Sensory Neurons

Nicotinic Regulation of Energy Homeostasis

Alpha9 nicotinic acetylcholine receptors and the treatment of pain

Contact Info

Product

Resources

About