Expression of nicotinic acetylcholine receptor subtypes in brain and retina

Whiting, Paul J.; Schoepfer, Ralf; Conroy, William G.; Gore, Martin; Keyser, Kent T.; Shimasaki, Shunichi; Esch, Frederick; Lindstrom, Jon

doi:10.1016/0169-328x(91)90057-5

Cited by 110 publications

(80 citation statements)

References 45 publications

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“…On the other hand, the receptors containing the ␣6 subunit are highly up-regulated during development, and their number increases 7.3 times between P1 and P21, when they become largely predominant over ␣3-containing receptors. Because the amino acid sequence of the ␣3 subunit is very close to that of the ␣6 subunit (70% identity), it is likely that most of the retinal receptors in adult vertebrates identified previously as containing ␣3 on the basis of immunolocalization and immunopurification experiments may actually have contained ␣6 rather than ␣3 subunits (Whiting et al, 1991;Keyser et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Subtypes Expression during Rat Retina Development and Their Regulation by Visual Experience

Moretti

Vailati²,

Zoli³

et al. 2004

Mol Pharmacol

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By acting through retinal nicotinic acetylcholine receptors (nAChRs), acetylcholine plays an important role in the development of both the retina and central visual pathways. Ligand binding and immunoprecipitation studies with subunit-specific antibodies showed that the expression of ␣Bungarotoxin (␣Bgtx) and high-affinity epibatidine (Epi) receptors is regulated developmentally and increases until postnatal day 21 (P21). The increase in Epi receptors is caused by a selective increase in the subtypes containing the ␣2, ␣4, ␣6, ␤2, and ␤3 subunits. Immunopurification studies revealed three major populations of Epi receptors on P21: ␣6* receptors (26%), which contain the ␣6␤3␤2, ␣6␣4␤3␤2, and ␣6␣3/␣2␤3␤2 subtypes; ␣4(non-␣6)* receptors (60%), which contain the ␣2␣4␤2 and ␣4␤2 subtypes; and (non-␣4/non-␣6)* receptors (14%), which contain the ␣2␤2/␤4 and ␣3␤2/␤4 subtypes. These three populations can be pharmacologically discriminated using ␣conotoxin MII, which binds the ␣6* population with high affinity. In situ hybridization showed that the transcripts for all of the subunits are heterogeneously distributed throughout retinal neurons at P21, with ␣3, ␣6, and ␤3 transcripts preferentially concentrated in the ganglion cell layer, ␣5 in the inner nuclear layer, and ␣4 and ␤2 distributed rather homogeneously. To investigate whether nAChR expression is affected by visual experience, we also studied dark-reared P21 rats. Visual deprivation had no effect on the expression of ␣Bgtx receptors or the developmentally regulated Epi receptors containing the ␣2, ␣6, and/or ␤3 subunits but significantly increased the expression of the Epi receptors containing the ␣4 and ␤2 subunits. Overall, this study demonstrates that the retina is the rat neural region that expresses the widest array of nAChR subtypes. These receptors have a specific distribution, and their expression is finely regulated during development and by visual experience.The nicotinic acetylcholine receptors (nAChRs) in vertebrate retina play a role in signaling at the earliest stages of development (long before there is any evidence of synaptic transmission) and also later during neuronal growth and synaptogenesis (Zhou, 2001;Feller, 2002). Neuronal nAChRs are cationic channels whose opening is physiologically controlled by acetylcholine (ACh) neurotransmitter. They form a heterogeneous family of pentameric oligomers made up of combinations of subunits encoded by at least 12 different genes. Although there are many subtypes consisting of different subunits, depending on their phylogenetic, functional, and pharmacological properties (Gotti et al., 1997a;Corringer et al., 2000;Hogg et al., 2003), two main classes have been identified: the ␣Bungarotoxin (␣Bgtx)-sensitive receptors made up of the ␣7, ␣8, ␣9, and/or ␣10 subunits, which can form homomeric or heteromeric receptors; and the ␣Bgtx-insensitive receptors consisting of the ␣2 to ␣6 and ␤2 to ␤4 subunits, which only form heteromeric receptors that bind epibatidine (Epi) with a high affinity. The number ...

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Section: Discussionmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Subtypes Expression during Rat Retina Development and Their Regulation by Visual Experience

Moretti

Vailati²,

Zoli³

et al. 2004

Mol Pharmacol

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“…mAb 210 Tzartos et al, 1987;Wang et al, 1996) was used to test for the presence of α3/α5-nAChRs; mAb 313 (Whiting et al, 1991) was used to test for α3-A. L. Obaid and others Nicotinic receptors in guinea-pig gut nAChRs; mAb 299 (Whiting and Lindstrom, 1988) was used to test for α4-nAChRs; mAb 295 (Whiting and Lindstrom, 1988) was used to test for β2-nAChRs; and mAb 337 (Nelson et al, 2001) was used to test for β4-nAChRs.…”

Section: Liquid-phase Riasmentioning

confidence: 99%

Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system

Obaid

Nelson

Lindstrom

et al. 2005

Journal of Experimental Biology

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ErratumObaid, A. L., Nelson, M. E., Lindstrom, J. and Salzberg, B. M. (2005). Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system. J. Exp. Biol. 208, 2981-3001. In the original published on-line version of this paper, the acceptance date was incorrect. It should have read 2 June 2005. The error has been rectified and the current on-line version and print versions are correct.We apologise to authors and readers for any inconvenience this may have caused. 2981Decoding the structure and function of native nicotinic acetylcholine receptors (nAChRs) is complex. Although the expression of defined combinations of nAChR-subunits in Xenopus oocytes permits the comparison of pharmacological properties of individual nAChR-subtypes, single neurones often express more than one subtype, making the physiological roles of nAChRs in intact neuronal networks difficult to assess (Colquhoun and Patrick, 1997). The function of a given nAChR depends upon its pre-, post-or peri-synaptic location as well as the activity of neighbouring non-nicotinic receptors. In addition, the properties of any neuronal ensemble depend not only on the intrinsic conductances of its neurones and the specific attributes of its many synapses but also on the complex and nonlinear dynamic interactions that result from the multiple parallel connectivity of its component cells (Parsons et al., 1991). Therefore, to understand nicotinic responses at the network level, it is necessary to record at high spatial and temporal resolution to characterize the behaviour of individual neurones and at lower spatial resolution to capture a panoramic view of network activity and to assess the directionality of the nicotinic pathways along the circumferential as well as the longitudinal axes.The enteric nervous system (ENS) regulates most gastrointestinal functions. Its neurones are clustered in ganglia that interconnect to form distinct plexuses in the gut wall: the myenteric plexus lies between the longitudinal and circular muscle layers, and the submucous plexus between the circular muscle layer and the mucosa. The behaviour of the effector Nicotinic transmission in the enteric nervous system (ENS) is extensive, but the role of individual nicotinic acetylcholine receptor (nAChR) subtypes in the functional connectivity of its plexuses has been elusive. Using monoclonal antibodies (mAbs) against neuronal α3-, α4-, α3/α5-, β2-, β4-and α7-subunits, combined with radioimmunoassays and immunocytochemistry, we demonstrate that guinea-pig enteric ganglia contain all of these nAChR-subunits with the exception of α4, and so, differ from mammalian brain. This information alone, however, is insufficient to establish the functional role of the identified nAChR-subtypes within the enteric networks and, ultimately, their specific contributions to gastrointestinal physiology. We have used voltagesensitive dyes and a high-speed CCD camera, in conjunction with specific antagonists to various nAChRs, to elucidate some of the distinct cont...

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“…2), on other subtypes of neuronal nAChR were also investigated. To this purpose the ␣4 nAChR subunit, which is abundant in the central nervous system (Whiting et al, 1991), and the ␣3 nAChR subunit, which is strongly expressed in autonomic ganglia (see De Biasi, 2002), were coexpressed with the ␤2 or the ␤4 nAChR subunit in Xenopus oocytes. The effects were assessed in voltage clamp experiments in which various concentrations of the three carbamates were coapplied with a near maximum-effective concentration (0.3-1 mM) of ACh to oocytes expressing the distinct nAChR subtypes.…”

Section: Selectivity Of Carbamate Effects For Distinct Subtypes Of Nementioning

confidence: 99%

Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase

Smulders

Bueters²,

Kleef

et al. 2003

Toxicology and Applied Pharmacology

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Effects of commonly used carbamate pesticides on rat neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. The potencies of these effects have been compared to the potencies of the carbamates to inhibit rat brain acetylcholinesterase. The potency order of six carbamates to inhibit ␣4␤4 nicotinic receptors is fenoxycarb Ͼ EPTC Ͼ carbaryl, bendiocarb Ͼ propoxur Ͼ aldicarb with IC50 values ranging from 3 M for fenoxycarb to 165 M for propoxur and Ͼ1 mM for aldicarb. Conversely, the potency order of these carbamates to inhibit rat brain acetylcholinesterase is bendiocarb Ͼ propoxur, aldicarb Ͼ carbaryl Ͼ Ͼ EPTC, fenoxycarb with IC50 values ranging from 1 M for bendiocarb to 17 M for carbaryl and Ͼ Ͼ1 mM for EPTC and fenoxycarb. The ␣4␤2, ␣3␤4, and ␣3␤2 nicotinic acetylcholine receptors are inhibited by fenoxycarb, EPTC, and carbaryl with potency orders similar to that for ␣4␤4 receptors. Comparing the potencies of inhibition of the distinct subtypes of nicotinic acetylcholine receptors shows that the ␣3␤2 receptor is less sensitive to inhibition by fenoxycarb and EPTC. The potency of inhibition depends on the carbamate as well as on a combination of ␣ and ␤ subunit properties. It is concluded that carbamate pesticides affect different subtypes of neuronal nicotinic receptors independently of acetylcholinesterase inhibition. This implicates that neuronal nicotinic receptors are additional targets for some carbamate pesticides and that these receptors may contribute to carbamate pesticide toxicology, especially after long-term exposure.

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Expression of nicotinic acetylcholine receptor subtypes in brain and retina

Cited by 110 publications

References 45 publications

Nicotinic Acetylcholine Receptor Subtypes Expression during Rat Retina Development and Their Regulation by Visual Experience

Nicotinic Acetylcholine Receptor Subtypes Expression during Rat Retina Development and Their Regulation by Visual Experience

Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system

Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase

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