A calmodulin inhibitor with high specificity compound 48/80, inhibits axonal transport in frog nerves without disruption of axonal microtubules
(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.
(Less)
- author
- Ekström, Per LU ; Wallin, Maria ; Kanje, M. LU and Edström, Anders LU
- organization
- publishing date
- 1991
- type
- 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
-
- pmid:1715113
- 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
- 2025-01-12 17:05:54
@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 (> 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}},
keywords = {{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}},
}