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

D L Ridley, A Rogers, S Wonnacott

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54 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1286-1295
Number of pages10
JournalBritish Journal of Pharmacology
Volume133
Issue number8
DOIs
Publication statusPublished - 2001

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