Differential Regulation Of Nicotinic Acetylcholine Receptor Expression By Human Te671/Rd Cells Following Second Messenger Modulation And Sodium Butyrate Treatments

Department

neurobiology

Document Type

Article

Abstract

Effects of second messenger system modulation and sodium butyrate (NaBu) treatment on nicotinic acetylcholine receptor (nAChR) expression by cells of the TE671/RD human clone were established. Treatment with dibutyryl cyclic adenosine 3′:5′-monophosphate (dbcAMP) or other substances that increase cellular cAMP content induces a 70% loss of nAChR per unit of membrane protein as assessed by binding studies using 125I-labeled α-bungarotoxin (I-Bgt). By contrast, phorbol 12-myristate-13-acetate (PMA) treatment induces an initial 50% decrease, and then a later two- to threefold increase, in I-Bgt binding sites. These PMA effects are temporally distinct from a PMA treatment-induced 50% downregulation of membrane-bound phorbol ester binding sites, are blocked by treatment of cells with the putative protein kinase C inhibitors H7 or trifluoroperazine, and are sensitive to the protein synthesis inhibitor cycloheximide and the topoisomerase inhibitor novobiocin. Treatment with both PMA and dbcAMP induces a threefold increase in nAChR expression, whereas treatment with NaBu alone or with PMA induces an 80% decrease in I-Bgt binding site expression. All of these effects are dose and time dependent and reflect changes in the number of binding sites rather than changes in nAChR afnity for I-Bgt. These data indicate involvement of both cAMP and C-kinase pathways in the regulation of nAChR expression in ways that are not simply additive, possibly due to cross-talk between second messenger pathways. In addition, transcriptional and/or translational events are implicated in PMA and NaBu effects. The results indicate a multiplicity in the effects and mechanisms involved in regulation of nAChR expression. © 1991.

Publication Date

1-1-1991

Publication Title

Molecular and Cellular Neuroscience

ISSN

10447431

Volume

2

Issue

1

First Page

52

Last Page

65

Digital Object Identifier (DOI)

10.1016/1044-7431(91)90039-Q

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