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Differential effects of chronic drug treatment on alpha 3*and alpha 7 nicotinic receptor binding sites, in hippocampal neurones and SH-SY5Y cells


Reference:

Ridley, D. L., Rogers, A. and Wonnacott, S., 2001. Differential effects of chronic drug treatment on alpha 3*and alpha 7 nicotinic receptor binding sites, in hippocampal neurones and SH-SY5Y cells. British Journal of Pharmacology, 133 (8), pp. 1286-1295.

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Official URL:

http://dx.doi.org/10.1038/sj.bjp.0704207

Abstract

1 The aim of this study was to compare the effects of chronic treatment (for 4 or 7 days) with nicotinic drugs and 20 mM KCl on numbers of surface alpha7 nicotinic AChR, identified by [I-125]-alpha bungarotoxin (alpha -Bgt) binding, in primary hippocampal cultures and SH-SY5Y cells. Numbers of alpha3* nicotinic AChR were also examined in SH-SY5Y cells, using [H-3]-epibatidine, which is predicted to label the total cellular population of predominantly alpha3 beta2* nicotinic AChR under the conditions used. 2 All the nicotinic agonists examined. the antagonists d-tubocurarine and methyllycaconitine, and KCl, upregulated[I-125]-alpha Bgt binding sites by 20-60% in hippocampal neurones and, where examined. SH-SY5Y cells. 3 Upregulation of [I-125]-alpha -Bgt binding sites by KCl was prevented by co-incubation with the L-type Ca2+ channel blocker verapamil or the Ca2+-calmodulin dependent kinase II (CaM-kinase II) inhibitor KN-62. Upregulation of [I-125]-alpha -Bgt binding sites by nicotine or 3,[(4-dimethylamino) cinnamylidene] anabaseine maleate (DMAC) was insensitive to these agents. 4 [H-3]-Epibatidine binding sites in SH-SY5Y cells were not affected by KCI but were upregulated in a verapamil-insensitive manner by nicotine and DMAC. KN-62 itself provoked a 2 fold increase in [H-3]-epibatidine binding. The inactive analogue KN-04 had no effect, suggesting that CaM-kinase II plays a role in regulating numbers of alpha3* nicotinic AChR. 5 These data indicate that numbers of alpha3* and alpha7 nicotinic AChR are modulated differently. Nicotinic agonists and KCI upregulate alpha7 nicotinic AChR through distinct cellular mechanisms, the latter involving L-type Ca2+ channels and CaM-kinase II. In contrast, alpha3* nicotinic AChR are not upregulated by KCI. This difference may reflect the distinct physiological roles proposed for alpha7 nicotinic AChR.

Details

Item Type Articles
CreatorsRidley, D. L., Rogers, A. and Wonnacott, S.
DOI10.1038/sj.bjp.0704207
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code4313

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