Interaction of pumiliotoxin B with an "alkaloid-binding domain" on the voltage-dependent sodium channel
The alkaloid pumiliotoxin B (PTX-B) "activates" voltage-dependent sodium channels in synaptoneurosomes and neuroblastoma cells. It appears that PTX-B activates sodium channels by interacting with a site that is allosterically coupled to other sites on the sodium channel, namely two scorpio...
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Published in | Molecular pharmacology Vol. 42; no. 6; pp. 1104 - 1108 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.12.1992
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Subjects | |
Online Access | Get full text |
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Summary: | The alkaloid pumiliotoxin B (PTX-B) "activates" voltage-dependent sodium channels in synaptoneurosomes and neuroblastoma cells.
It appears that PTX-B activates sodium channels by interacting with a site that is allosterically coupled to other sites on
the sodium channel, namely two scorpion toxin sites and the brevetoxin site. In guinea pig cortical synaptoneurosomes, alpha-scorpion
toxin, beta-scorpion toxin, and brevetoxin induce a dose-dependent potentiation of PTX-B-induced 22Na+ influx. The synergism
with beta-scorpion toxin differentiates PTX-B from the alkaloid veratridine, which induces an activation of sodium channels
that is not affected by beta-scorpion toxin. PTX-B does not inhibit [3H]batrachotoxinin-A benzoate ([3H]BTX-B) binding to
the alkaloid site on sodium channels. On the other hand, aconitine, which activates sodium channels and inhibits [3H]BTX-B
binding, induces a 22Na+ influx that, like PTX-B-induced 22Na+ influx, is potentiated by alpha-scorpion toxin, beta-scorpion
toxin, and brevetoxin. Inhibition of [3H]BTX-B binding by aconitine is reduced in the presence of PTX-B. Both a type I pyrethroid
(allethrin) and a type II pyrethroid (fenvalerate) inhibit PTX-B- and PTX-B/alpha-scorpion toxin-mediated 22Na+ influx. Allethrin
and fenvalerate also inhibit aconitine-mediated 22Na+ flux but not BTX-mediated 22Na+ influx. It is proposed that on the sodium
channel there is an "alkaloid-binding domain" at which alkaloids exert stimulatory actions. However, depending on the region
on the domain to which the binding occurs, different allosteric interactions with other sites can be observed. PTX-B is proposed
to interact with a part of the alkaloid-binding domain that is shared by aconitine but not by batrachotoxin or veratridine,
whereas aconitine interacts with a part of the domain shared by PTX-B and by batrachotoxin/veratridine. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0026-895X 1521-0111 |