Nicotinic receptors in sensory ganglia

Polz-Tejera, Gertraud; Hunt, Stephen P.; Schmidt, John T.

doi:10.1016/0006-8993(80)90881-1

Cited by 27 publications

(4 citation statements)

References 11 publications

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“…2002). Confirming previous studies with radioactive αBgt and autoradiography (Ninkovic and Hunt 1983; Polz‐Tejera et al. 1980), we observed Alexa‐αBgt labeling of a subpopulation of preferentially large DRG neurons.…”

Section: Discussionsupporting

confidence: 90%

Presence of α7 nicotinic acetylcholine receptors on dorsal root ganglion neurons proved using knockout mice and selective α‐neurotoxins in histochemistry

Shelukhina¹,

Kryukova²,

Lips³

et al. 2009

Journal of Neurochemistry

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Nicotinic acetylcholine receptors (nAChRs) are ligand-gated pentameric ion channels. They are subdivided into muscleand neuronal types depending on tissues where they were first discovered. The muscle nAChRs consisting of a-, b-, c-(or e-) and d-subunits are situated at motor end plates of skeletal muscle where they mediate neuromuscular transmission. The neuronal nAChRs are widely distributed in the nervous system (Gotti et al. 2007). Certain neuronal subunits, such as a7, a8 or a9, can form both homopentameric and heteropentameric (a7a8, a9a10) channels, while most other neuronal nAChRs are heteropentameric composed of a(a2-a7)-and b(b2-b4)-subunit combinations. Subunit composition determines preferred ion permeability (mono-vs. divalent cations), ligand binding (e.g. affinity to choline) and receptor desensitization characteristics (Lindstrom et al. 1995). Hence, deciphering nAChRs subunit composition is a necessary step in understanding their function.In complex tissues where multiple subtypes of nAChRs are expressed by different cell populations, accurate subunit analysis cannot be achieved by biochemical assays of tissue homogenates. The most popular tool for investigation of nicotinic acetylcholine receptor (nAChR) subunit distribution Abbreviations used: a7 KO, a7 nAChR subunit knockout; aBgt, abungarotoxin; Alexa-aBgt, Alexa Fluor 488-conjugated aBgt; BSA, bovine serum albumin; CTX, a-cobratoxin; DRG, dorsal root ganglion; KO, knockout; nAChR, nicotinic acetylcholine receptor; NTII, a-neurotoxin II; PBS, phosphate-buffered saline; PEI, polyethyleneimine; WT, wild type. AbstractIn complex tissues where multiple subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed, immunohistochemistry has been the most popular tool for investigation of nAChR subunit distribution. However, recent studies with nAChR subunit knockout mice demonstrated that a large panel of antibodies is unsuitable. Thus, we aimed to develop a histochemical method for selective labeling of a7 nAChR with neurotoxins, utilizing a7 nAChR-transfected cells, dorsal root ganglia (DRG) and spinal cord from wild-type and knockout mouse. The specificity of Alexa Fluor 488-conjugated a-bungarotoxin (Alexa-aBgt) was demonstrated in binding to a7-transfected cells inhibited by long-chain a-cobratoxin (CTX), but not short-chain a-neurotoxin II (NTII). In contrast, binding to Torpedo muscle-type nAChRs and to motor end plates in mouse tongue sections was prevented by both CTX and NTII. In tissue sections of DRG, expressing all neuronal nAChR subunits, only CTX precluded Alexa-aBgt labeling of neurons, with no staining for a7 nAChR knockout tissue. It proved that a7 nAChRs are the major aBgt-binding sites in mouse DRG. Corresponding results were obtained for terminals in the spinal cord. Thus, we present a protocol utilizing Alexa-aBgt and non-labeled CTX/NTII that allows specific histochemical detection of a7 nAChR with a spatial resolution at the level of single axon terminals.

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Section: Discussionsupporting

confidence: 90%

Presence of α7 nicotinic acetylcholine receptors on dorsal root ganglion neurons proved using knockout mice and selective α‐neurotoxins in histochemistry

Shelukhina¹,

Kryukova²,

Lips³

et al. 2009

Journal of Neurochemistry

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“…Other sensory systems Dorsal root ganglion cells give rise to a single process that divides and sends one branch to the periphery and one to the spinal cord. Some of these cells bind CrBgt (Polz-Tejera et al, 1980) and stain for AChE (Kokko, 1965), and we found that a subpopulation of these neurons (both small and large) also stains with mAb 270 (Fig. 2P), as do ganglion cells in the trigeminal ganglion ( Fig.…”

Section: Immunolabeling In Chicken Brainmentioning

confidence: 68%

Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system

et al. 1987

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The distribution of nicotinic acetylcholine receptors (AChR) in the rat and mouse central nervous system has been mapped in detail using monoclonal antibodies to receptors purified from chicken and rat brain. Initial studies in the chicken brain indicate that different neuronal AChRs are contained in axonal projections to the optic lobe in the midbrain from neurons in the lateral spiriform nucleus and from retinal ganglion cells. Monoclonal antibodies to the chicken and rat brain AChRs also label apparently identical regions in all major subdivisions of the central nervous system of rats and mice, and this pattern is very similar to previous reports of 3H-nicotine binding, but quite different from that of alpha-bungarotoxin binding. In several instances, the immunohistochemical evidence has strongly indicated that neuronal AChR undergoes axonal transport. The clearest example of this has been in the visual system, where labeling was observed in the retina, the optic nerve and tract, and in all of the major terminal fields of the optic nerve except the ventral suprachiasmatic nucleus. This was confirmed in unilateral enucleation experiments in the rat, where labeling was greatly reduced in the contralateral optic tract, ventral lateral geniculate nucleus, pretectal nuclei receiving direct visual input, superficial layers of the superior colliculus, and medical terminal nucleus, and was significantly reduced in the dorsal lateral geniculate nucleus. Clear neuronal labeling was also observed in dorsal root ganglion cells and in cranial nerve nuclei containing motoneurons that innervate branchial arch-derived muscles, although the possibility that neuronal AChR undergoes axonal transport in the latter cells was not tested experimentally.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Although to date this phenomenon has not been demonstrated in vivo, both binding and electrophysiological findings provide evidence that (-)-nicotine and capsaicin both activate a subset of sensory afferents. Binding studies have described the identification of specific cr-bungarotoxin binding sites on DRG (Polz-Tejera et al, 1980), which have been reported to be reduced following capsaicin treatment , and electrophysiological studies have demonstrated that (-)-nicotine and capsaicin both activate a subset of sensory afferents in trigeminal ganglion (Liu and Simon, 1996). From these observations, the antinociceptive actions of ChCAs may be explained by the ability of ChCAs to deplete stores of nociceptive peptides, such as SP, and/or desensitize sensory neurons to noxious stimuli.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Nicotinic Receptors Potentially Modulating Nociceptive Transmission at the Level of the Primary Sensory Neuron: Studies with F11 Cells

Puttfarcken

Manelli

Arnerić

et al. 1997

Journal of Neurochemistry

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F11 cells are a dorsal root ganglion (DRG) cell line used to model the function of authentic type C, peptidergic, nociceptive neurons. The cellular events underlying the antinociceptive effects of (±)‐epibatidine, a nicotinic acetylcholine receptor (nAChR) ligand that is 200‐fold more potent than morphine, is unknown. The present study investigated the ability of cholinergic channel activators (ChCAs) to effect nAChR‐gated ion flux and modulate the release of substance P (SP), a neuropeptide identified to play a critical role in nociception. The prototypical agonists (−)‐nicotine and (−)‐cytisine, the ganglionic stimulant 1,1‐dimethyl‐4‐phenylpiperazinium, the novel ChCA ABT‐418 [(S)‐3‐methyl‐5‐(‐1‐methyl‐2‐pyrrolidinyl)isoxazole], and (±)‐epibatidine evoked a concentration‐dependent stimulation of rubidium (86Rb+) efflux with EC50 values of 14.2 ± 1.6, 63.4 ± 24, 3.8 ± 2.0, 29.8 ± 2.6, and 0.019 ± 0.001 µM as well as maximal intrinsic activities of 100, 97, 69, 75, and 102%, respectively. The noncompetitive nAChR antagonist mecamylamine potently antagonized (−)‐nicotine‐evoked ion flux, whereas the competitive antagonist dihydro‐β‐erythroidine was a weak antagonist, giving support to an α3β4 nAChR subtype. In addition, concentrations of (±)‐epibatidine, similar to those necessary to induce maximal 86Rb+ efflux, evoked spontaneous release of SP from these cells, which was blocked by mecamylamine. Furthermore, prolonged exposure to (±)‐epibatidine desensitized the functional response of the nAChR in this cell line (IC50 = 12 ± 9 nM). These findings in F11 cells provide a model to investigate the role nAChRs play in modulating DRG cell function, and may lead to insights into the role these receptors have in modulating nociceptive transmission.

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Nicotinic receptors in sensory ganglia

Cited by 27 publications

References 11 publications

Presence of α7 nicotinic acetylcholine receptors on dorsal root ganglion neurons proved using knockout mice and selective α‐neurotoxins in histochemistry

Presence of α7 nicotinic acetylcholine receptors on dorsal root ganglion neurons proved using knockout mice and selective α‐neurotoxins in histochemistry

Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system

Evidence for Nicotinic Receptors Potentially Modulating Nociceptive Transmission at the Level of the Primary Sensory Neuron: Studies with F11 Cells

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