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Involvement of the alpha3 subunit in central nicotinic binding populations.


ABSTRACT: The alpha3 subunit gene was one of the first neuronal nicotinic acetylcholine receptor (nAChR) subunits to be cloned (Boulter et al., 1986), but direct evidence of alpha3 subunit contributions to mammalian central nAChR populations has not been presented. The studies reported here used mice engineered to contain a null mutation in the alpha3 nAChR subunit gene (Xu et al., 1999) to examine the involvement of the alpha3 subunit in central nAChR populations. Heterologously expressed alpha3beta2 and alpha3beta4 nAChRs are pharmacologically similar to native [125I]alpha-conotoxin MII (alpha-CtxMII)-binding and 3-(2(S)-azetidinylmethoxy)pyridine dihydrochloride (A85380)-resistant [125I]epibatidine-binding nAChR subtypes, respectively. The hypothesis that both native sites are alpha3-subtype nAChRs was tested using quantitative autoradiography in alpha3-null mutant mice. Somewhat surprisingly, deletion of the alpha3 nAChR subunit gene did not affect expression of the great majority of [125I]alpha-CtxMII-binding sites, indicating that they do not correspond to heterologously expressed alpha3beta2 nAChRs. The only exception to this was observed in the habenulointerpeduncular tract, where alpha3-dependent [125I]alpha-CtxMII binding was observed. This finding may suggest the presence of an additional, minor nicotinic population in this pathway. In contrast, most -resistant [125I]epibatidine-binding nAChRs were dependent on alpha3 gene expression, suggesting that they do indeed correspond to an alpha3 nAChR subtype. However, widespread but lower levels of alpha3-independent -resistant [125I]epibatidine binding were also seen. Again, this may indicate the existence of an additional, minor population of non-alpha3 -resistant sites.

SUBMITTER: Whiteaker P 

PROVIDER: S-EPMC6758302 | BioStudies | 2002-01-01

REPOSITORIES: biostudies

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