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A calmodulin inhibitor with high specificity compound 48/80, inhibits axonal transport in frog nerves without disruption of axonal microtubules

Ekström, Per LU ; Wallin, Maria; Kanje, M. LU and Edström, Anders LU (1991) In Acta Physiologica Scandinavica 142(2). p.181-189
Abstract

The calmodulin inhibitor compound 48/80 has previously been shown to arrest axonal transport in vitro in the regenerating frog sciatic nerve. The inhibition was limited to the outgrowth region of nerves, which had been allowed to regenerate in vivo for 6 days after a crush lesion, before they were incubated with or without drugs in vitro overnight. The effects of compound 48/80 on the regenerating nerve were further investigated. A concentration of compound 48/80 (50 μg ml-1), which effectively inhibits axonal transport, did not cause observable changes of the microtubules of regenerating axons in the outgrowth region as judged by electron microscopy. Furthermore, it was shown that also a lower concentration (25 μg... (More)

The calmodulin inhibitor compound 48/80 has previously been shown to arrest axonal transport in vitro in the regenerating frog sciatic nerve. The inhibition was limited to the outgrowth region of nerves, which had been allowed to regenerate in vivo for 6 days after a crush lesion, before they were incubated with or without drugs in vitro overnight. The effects of compound 48/80 on the regenerating nerve were further investigated. A concentration of compound 48/80 (50 μg ml-1), which effectively inhibits axonal transport, did not cause observable changes of the microtubules of regenerating axons in the outgrowth region as judged by electron microscopy. Furthermore, it was shown that also a lower concentration (25 μg ml-1) inhibited axonal transport. As a measure of possible metabolic effects, the level of ATP was assessed in the regenerating nerve after exposure to compound 48/80. Compound 48/80 at 25 μg ml-1 did not change the level of ATP in the nerve. The assembly of bovine brain microtubule proteins in a cell-free system was unaffected by 25 μg ml-1 of compound 48/80 and slightly inhibited by 50 μg ml-1. At higher concentrations (> 100 μg ml-1) assembly of microtubules appeared stimulated, and microtubule spirals as well as closely aligned microtubules could be seen. These effects appeared to be unrelated to the transport effects. The present results indicate that compound 48/80 arrests axonal transport via mechanisms other than destruction of axonal microtubules or interference with the energy metabolism. It is possible that these mechanisms involve inhibition of calmodulin-regulated events essential to the transport.

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Contribution to journal
publication status
published
subject
keywords
axonal transport, calmodulin, compound 48/80, frog sciatic nerve, microtubule proteins, microtubules
in
Acta Physiologica Scandinavica
volume
142
issue
2
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:0025765539
ISSN
0001-6772
language
English
LU publication?
yes
id
5fea66fd-c20a-486d-a6f5-4a49440db675
date added to LUP
2016-12-07 14:35:35
date last changed
2017-01-01 08:42:27
@article{5fea66fd-c20a-486d-a6f5-4a49440db675,
  abstract     = {<p>The calmodulin inhibitor compound 48/80 has previously been shown to arrest axonal transport in vitro in the regenerating frog sciatic nerve. The inhibition was limited to the outgrowth region of nerves, which had been allowed to regenerate in vivo for 6 days after a crush lesion, before they were incubated with or without drugs in vitro overnight. The effects of compound 48/80 on the regenerating nerve were further investigated. A concentration of compound 48/80 (50 μg ml<sup>-1</sup>), which effectively inhibits axonal transport, did not cause observable changes of the microtubules of regenerating axons in the outgrowth region as judged by electron microscopy. Furthermore, it was shown that also a lower concentration (25 μg ml<sup>-1</sup>) inhibited axonal transport. As a measure of possible metabolic effects, the level of ATP was assessed in the regenerating nerve after exposure to compound 48/80. Compound 48/80 at 25 μg ml<sup>-1</sup> did not change the level of ATP in the nerve. The assembly of bovine brain microtubule proteins in a cell-free system was unaffected by 25 μg ml<sup>-1</sup> of compound 48/80 and slightly inhibited by 50 μg ml<sup>-1</sup>. At higher concentrations (&gt; 100 μg ml<sup>-1</sup>) assembly of microtubules appeared stimulated, and microtubule spirals as well as closely aligned microtubules could be seen. These effects appeared to be unrelated to the transport effects. The present results indicate that compound 48/80 arrests axonal transport via mechanisms other than destruction of axonal microtubules or interference with the energy metabolism. It is possible that these mechanisms involve inhibition of calmodulin-regulated events essential to the transport.</p>},
  author       = {Ekström, Per and Wallin, Maria and Kanje, M. and Edström, Anders},
  issn         = {0001-6772},
  keyword      = {axonal transport,calmodulin,compound 48/80,frog sciatic nerve,microtubule proteins,microtubules},
  language     = {eng},
  number       = {2},
  pages        = {181--189},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica Scandinavica},
  title        = {A calmodulin inhibitor with high specificity compound 48/80, inhibits axonal transport in frog nerves without disruption of axonal microtubules},
  volume       = {142},
  year         = {1991},
}