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Physostigmine and galanthamine: probes for a novel binding site on the alpha 4 beta 2 subtype of neuronal nicotinic acetylcholine receptors stably expressed in fibroblast cells.
J Pharmacol Exp Ther. 1994 Aug; 270(2):768-78.JP

Abstract

In the present study, we demonstrated that the chicken alpha 4 beta 2 neuronal nicotinic receptor stably expressed in transfected mouse fibroblasts (M10 cells) can be activated via the acetylcholine-binding site or via a site that is distinct from that for acetylcholine and recognizes physostigmine and galanthamine as agonists. In outside-out patches excised from dexamethasone-induced M10 cells, (+)-anatoxin-a, physostigmine and galanthamine (each at 1 microM) activated single channels with conductances of 18 and 30 pS. Dihydro-beta-erythroidine (1-30 nM), but not the nicotinic receptor-specific monoclonal antibody FK1, reduced the frequency of channels activated by anatoxin (1 microM). On the other hand, the frequency of channel activity induced by physostigmine (1 microM) was unaffected by dihydro-beta-erythroidine and was markedly decreased by FK1. In uninduced M10 cells and in dexamethasone-treated untransfected fibroblasts, we observed that physostigmine, galanthamine and nicotinic agonists did not evoke whole-cell or single-channel currents. Also, neither [3H]L-nicotine nor FK1 was able to bind to uninduced M10 cells. In dexamethasone-induced M10 cells, the nicotinic agonists acetylcholine, anatoxin, 1,1-dimethyl-4-phenylpiperazinium, (-)-nicotine, and cytisine (each at 100 microM) activated whole-cell currents that showed a marked inward rectification and were sensitive to blockade by dihydro-beta-erythroidine (100 nM). However, neither galanthamine nor physostigmine could evoke whole-cell currents in cells that were responsive to nicotinic agonists. Other effects of physostigmine and galanthamine on the nicotinic receptor that outweight the agonist properties of these compounds could account for their inability to evoke whole-cell currents.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8071869

Citation

Pereira, E F., et al. "Physostigmine and Galanthamine: Probes for a Novel Binding Site On the Alpha 4 Beta 2 Subtype of Neuronal Nicotinic Acetylcholine Receptors Stably Expressed in Fibroblast Cells." The Journal of Pharmacology and Experimental Therapeutics, vol. 270, no. 2, 1994, pp. 768-78.
Pereira EF, Alkondon M, Reinhardt S, et al. Physostigmine and galanthamine: probes for a novel binding site on the alpha 4 beta 2 subtype of neuronal nicotinic acetylcholine receptors stably expressed in fibroblast cells. J Pharmacol Exp Ther. 1994;270(2):768-78.
Pereira, E. F., Alkondon, M., Reinhardt, S., Maelicke, A., Peng, X., Lindstrom, J., Whiting, P., & Albuquerque, E. X. (1994). Physostigmine and galanthamine: probes for a novel binding site on the alpha 4 beta 2 subtype of neuronal nicotinic acetylcholine receptors stably expressed in fibroblast cells. The Journal of Pharmacology and Experimental Therapeutics, 270(2), 768-78.
Pereira EF, et al. Physostigmine and Galanthamine: Probes for a Novel Binding Site On the Alpha 4 Beta 2 Subtype of Neuronal Nicotinic Acetylcholine Receptors Stably Expressed in Fibroblast Cells. J Pharmacol Exp Ther. 1994;270(2):768-78. PubMed PMID: 8071869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physostigmine and galanthamine: probes for a novel binding site on the alpha 4 beta 2 subtype of neuronal nicotinic acetylcholine receptors stably expressed in fibroblast cells. AU - Pereira,E F, AU - Alkondon,M, AU - Reinhardt,S, AU - Maelicke,A, AU - Peng,X, AU - Lindstrom,J, AU - Whiting,P, AU - Albuquerque,E X, PY - 1994/8/1/pubmed PY - 1994/8/1/medline PY - 1994/8/1/entrez SP - 768 EP - 78 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 270 IS - 2 N2 - In the present study, we demonstrated that the chicken alpha 4 beta 2 neuronal nicotinic receptor stably expressed in transfected mouse fibroblasts (M10 cells) can be activated via the acetylcholine-binding site or via a site that is distinct from that for acetylcholine and recognizes physostigmine and galanthamine as agonists. In outside-out patches excised from dexamethasone-induced M10 cells, (+)-anatoxin-a, physostigmine and galanthamine (each at 1 microM) activated single channels with conductances of 18 and 30 pS. Dihydro-beta-erythroidine (1-30 nM), but not the nicotinic receptor-specific monoclonal antibody FK1, reduced the frequency of channels activated by anatoxin (1 microM). On the other hand, the frequency of channel activity induced by physostigmine (1 microM) was unaffected by dihydro-beta-erythroidine and was markedly decreased by FK1. In uninduced M10 cells and in dexamethasone-treated untransfected fibroblasts, we observed that physostigmine, galanthamine and nicotinic agonists did not evoke whole-cell or single-channel currents. Also, neither [3H]L-nicotine nor FK1 was able to bind to uninduced M10 cells. In dexamethasone-induced M10 cells, the nicotinic agonists acetylcholine, anatoxin, 1,1-dimethyl-4-phenylpiperazinium, (-)-nicotine, and cytisine (each at 100 microM) activated whole-cell currents that showed a marked inward rectification and were sensitive to blockade by dihydro-beta-erythroidine (100 nM). However, neither galanthamine nor physostigmine could evoke whole-cell currents in cells that were responsive to nicotinic agonists. Other effects of physostigmine and galanthamine on the nicotinic receptor that outweight the agonist properties of these compounds could account for their inability to evoke whole-cell currents. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8071869/Physostigmine_and_galanthamine:_probes_for_a_novel_binding_site_on_the_alpha_4_beta_2_subtype_of_neuronal_nicotinic_acetylcholine_receptors_stably_expressed_in_fibroblast_cells_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8071869 DB - PRIME DP - Unbound Medicine ER -