Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors. / Mellor, I R; Brier, T J; Pluteanu, F; Strømgaard, K; Saghyan, A; Eldursi, N; Brierley, M J; Andersen, K; Jaroszewski, J W; Krogsgaard-Larsen, P; Usherwood, P N R.

In: Neuropharmacology, Vol. 44, No. 1, 01.2003, p. 70-80.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Mellor, IR, Brier, TJ, Pluteanu, F, Strømgaard, K, Saghyan, A, Eldursi, N, Brierley, MJ, Andersen, K, Jaroszewski, JW, Krogsgaard-Larsen, P & Usherwood, PNR 2003, 'Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors', Neuropharmacology, vol. 44, no. 1, pp. 70-80.

APA

Mellor, I. R., Brier, T. J., Pluteanu, F., Strømgaard, K., Saghyan, A., Eldursi, N., Brierley, M. J., Andersen, K., Jaroszewski, J. W., Krogsgaard-Larsen, P., & Usherwood, P. N. R. (2003). Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors. Neuropharmacology, 44(1), 70-80.

Vancouver

Mellor IR, Brier TJ, Pluteanu F, Strømgaard K, Saghyan A, Eldursi N et al. Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors. Neuropharmacology. 2003 Jan;44(1):70-80.

Author

Mellor, I R ; Brier, T J ; Pluteanu, F ; Strømgaard, K ; Saghyan, A ; Eldursi, N ; Brierley, M J ; Andersen, K ; Jaroszewski, J W ; Krogsgaard-Larsen, P ; Usherwood, P N R. / Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors. In: Neuropharmacology. 2003 ; Vol. 44, No. 1. pp. 70-80.

Bibtex

@article{8827aaf3e4cf4139b2f6b7a3b08d4c8a,
title = "Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors",
abstract = "Voltage-dependent, non-competitive inhibition by philanthotoxin-343 (PhTX-343) analogues, with reduced charge or length, of nicotinic acetylcholine receptors (nAChR) of TE671 cells and ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR)) expressed in Xenopus oocytes from rat brain RNA was investigated. At nAChR, analogues with single amine-to-methylene or amine-to-ether substitutions had similar potencies to PhTX-343 (IC(50)=16.6 microM at -100 mV) whereas PhTX-(12), in which both secondary amino groups of PhTX-343 were replaced by methylenes, was more potent than PhTX-343 (IC(50)=0.93 microM at -100 mV). Truncated analogues of PhTX-343 were less potent. Inhibition by all analogues was voltage-dependent. PhTX-343 (IC(50)=2.01 microM at -80 mV) was the most potent inhibitor of NMDAR. At AMPAR, most analogues were equipotent with PhTX-343 (IC(50)=0.46 microM at -80 mV), apart from PhTX-83, which was more potent (IC(50)=0.032 microM at -80 mV), and PhTX-(12) and 4,9-dioxa-PhTX-(12), which were less potent (IC(50)s>300 microM at -80 mV). These studies show that PhTX-(12) is a selective nAChR inhibitor and PhTX-83 is a selective AMPAR antagonist.",
keywords = "Animals, Cell Line, Humans, Muscle, Skeletal, Nicotinic Antagonists, Oocytes, Patch-Clamp Techniques, Phenols, Polyamines, Rats, Rats, Wistar, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate, Receptors, Nicotinic, Structure-Activity Relationship, Xenopus laevis",
author = "Mellor, {I R} and Brier, {T J} and F Pluteanu and K Str{\o}mgaard and A Saghyan and N Eldursi and Brierley, {M J} and K Andersen and Jaroszewski, {J W} and P Krogsgaard-Larsen and Usherwood, {P N R}",
year = "2003",
month = jan,
language = "English",
volume = "44",
pages = "70--80",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Pergamon Press",
number = "1",

}

RIS

TY - JOUR

T1 - Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors

AU - Mellor, I R

AU - Brier, T J

AU - Pluteanu, F

AU - Strømgaard, K

AU - Saghyan, A

AU - Eldursi, N

AU - Brierley, M J

AU - Andersen, K

AU - Jaroszewski, J W

AU - Krogsgaard-Larsen, P

AU - Usherwood, P N R

PY - 2003/1

Y1 - 2003/1

N2 - Voltage-dependent, non-competitive inhibition by philanthotoxin-343 (PhTX-343) analogues, with reduced charge or length, of nicotinic acetylcholine receptors (nAChR) of TE671 cells and ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR)) expressed in Xenopus oocytes from rat brain RNA was investigated. At nAChR, analogues with single amine-to-methylene or amine-to-ether substitutions had similar potencies to PhTX-343 (IC(50)=16.6 microM at -100 mV) whereas PhTX-(12), in which both secondary amino groups of PhTX-343 were replaced by methylenes, was more potent than PhTX-343 (IC(50)=0.93 microM at -100 mV). Truncated analogues of PhTX-343 were less potent. Inhibition by all analogues was voltage-dependent. PhTX-343 (IC(50)=2.01 microM at -80 mV) was the most potent inhibitor of NMDAR. At AMPAR, most analogues were equipotent with PhTX-343 (IC(50)=0.46 microM at -80 mV), apart from PhTX-83, which was more potent (IC(50)=0.032 microM at -80 mV), and PhTX-(12) and 4,9-dioxa-PhTX-(12), which were less potent (IC(50)s>300 microM at -80 mV). These studies show that PhTX-(12) is a selective nAChR inhibitor and PhTX-83 is a selective AMPAR antagonist.

AB - Voltage-dependent, non-competitive inhibition by philanthotoxin-343 (PhTX-343) analogues, with reduced charge or length, of nicotinic acetylcholine receptors (nAChR) of TE671 cells and ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR)) expressed in Xenopus oocytes from rat brain RNA was investigated. At nAChR, analogues with single amine-to-methylene or amine-to-ether substitutions had similar potencies to PhTX-343 (IC(50)=16.6 microM at -100 mV) whereas PhTX-(12), in which both secondary amino groups of PhTX-343 were replaced by methylenes, was more potent than PhTX-343 (IC(50)=0.93 microM at -100 mV). Truncated analogues of PhTX-343 were less potent. Inhibition by all analogues was voltage-dependent. PhTX-343 (IC(50)=2.01 microM at -80 mV) was the most potent inhibitor of NMDAR. At AMPAR, most analogues were equipotent with PhTX-343 (IC(50)=0.46 microM at -80 mV), apart from PhTX-83, which was more potent (IC(50)=0.032 microM at -80 mV), and PhTX-(12) and 4,9-dioxa-PhTX-(12), which were less potent (IC(50)s>300 microM at -80 mV). These studies show that PhTX-(12) is a selective nAChR inhibitor and PhTX-83 is a selective AMPAR antagonist.

KW - Animals

KW - Cell Line

KW - Humans

KW - Muscle, Skeletal

KW - Nicotinic Antagonists

KW - Oocytes

KW - Patch-Clamp Techniques

KW - Phenols

KW - Polyamines

KW - Rats

KW - Rats, Wistar

KW - Receptors, AMPA

KW - Receptors, N-Methyl-D-Aspartate

KW - Receptors, Nicotinic

KW - Structure-Activity Relationship

KW - Xenopus laevis

M3 - Journal article

C2 - 12559123

VL - 44

SP - 70

EP - 80

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 1

ER -

ID: 45823664