title: Differential regulation of nicotinic acetylcholine receptor expression by human TE671/RD cells following second messenger modulation and sodium butyrate treatments.
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 (125)I-labeled alpha-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.
authors.affiliation: Division of Neurobiology, Barrow Neurological Institute, 350 West Thomas Road, Phoenix, Arizona 85013, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bencherif
authors.forename: R J
authors.initials: RJ
authors.lastname: Lukas