| 1. |
- EDSTRÖM, Anders, et al.
(författare)
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Is protease activity involved in fast axonal transport?
- 1984
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 121:4, s. 379-384
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Tidskriftsartikel (refereegranskat)abstract
- N‐a‐p‐Tosyl‐L‐Lysine Chloromethyl Ketone (TLCK), a protease inhibitor, was found to irreversibly inhibit rapid axonal transport of protein in vitro in the frog sciatic nerve. TLCK exerted its action at the axonal level and seemed to depress the rate rather than the amount of transported protein. The efficiency of TLCK as a protease inhibitor was demonstrated by polyacrylamide gel electrophoresis, which showed that degradation of high molecular weight proteins (presumably neurofilament subunits) into a 25 000 dalton protein could be induced by exposing the frog nerves to triton‐X and prevented by the presence of TLCK. Findings that TLCK, at a transport inhibiting concentration (0.1 mM), had little or no effects on either protein synthesis or ATP levels, suggest that TLCK did not affect transport due to general cytotoxic properties. The effects of TLCK is discussed in relation to possible roles of protease activity in axonal transport.
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| 2. |
- EKSTRÖM, Per, et al.
(författare)
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Effects of phenothiazines and dibenzazepines on axonal transport and microtubule assembly in vitro
- 1982
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 116:2, s. 121-125
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Tidskriftsartikel (refereegranskat)abstract
- Various phenothiazines (thioridazine, trifluoperazine and chlorpromazine) and dibenzazepines (lofepramine, amitriptyline and desipramine) were studied for effects on fast axonal transport (AXT) in vitro in frog sciatic nerves. AXT, measured as the accumulation of (3H) leucine‐labelled proteins in front of a ligature, was inhibited by more then 50% by all the drugs tested at 0.2 mM concentrations. Thioridazine and lofepramine were the most potent inhibitors. These effects were not due to decreased ganglionic incorporation. Some of the drugs also reduced the levels of high energy phosphates, adenosinetriphosphate (ATP) and creatinephosphate (CrP), but not to an extent which is likely to explain the arrested AXT. The polymerization of purified brain tubulin was inhibited by the phenothiazines but unaffected by the dibenzazepines at concentrations which inhibited AXT. Phenothiazines and dibenzazepines are chemically related and known to have a high affinity for calmodulin. The possibility that these drugs interefere with calmodulin regulated processes of importance for AXT will be discussed.
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| 3. |
- Ekström, Per, et al.
(författare)
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Inhibition of Fast Axonal Transport by erythro‐9‐[3‐(2‐Hydroxynonyl)]Adenine
- 1984
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 43:5, s. 1342-1345
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: erythro‐9‐[3‐(2‐Hydroxynonyl)]adenine, an inhibitor of protein carboxylmethylation and dynein‐ATPase activity, inhibited fast axonal transport in vitro in frog sciatic nerves. Its site of action might be associated with an ATPase on which transport depends, since specific carboxylmethylation inhibitors lacked effects on transport. The levels of high energy phosphates and protein synthesis were unaffected by the drug at a transport‐inhibiting concentration, making disturbances due to metabolic effects less likely. An erythro‐9‐[3‐(2‐hy‐droxynonyl)]adenine‐sensitive ATPase was looked for in various nerve fractions but has so far not been resolved.
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| 4. |
- Kanje, Martin, et al.
(författare)
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Divalent cations and fast axonal transport in chemically desheathed (triton X-treated) frog sciatic nerve
- 1982
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Ingår i: Brain Research. - 0006-8993. ; 241:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the ability of divalent cations to restore to normal axonal transport (AXT) which was inhibited by deprivation of Ca2+ and/or Mg2+ ions. The epi- and perineurium of the frog sciatic nerve were damaged by a 30-s wash in Triton X-100 containing frog Ringer's. This treatment did not affect either AXT or nerve levels of Ca2+ and Mg2+, but made the ions more easily extractable with a Ca2+- and Mg2+-free Ringer's solution (CMFR). Inhibition of AXT was achieved by incubating Triton X-100-treated nerves in CMFR + EGTA for 5 h, followed by an additional incubation for 12 h in CMFR or Ringer's devoid of only Ca2+ (CFR). These treatments reduced Ca2+ and Mg2+ contents by 77% and 38% respectively. Addition of Ca2+ (1.1 mM) during the 12-h period stimulated AXT, measured as accumulation of 3H-labelled components in front of a ligature, several fold. Mg2+ could not substitute for Ca2+ but potentiated the stimulating effect of Ca2+. Addition of other divalent cations did not affect AXT (Sr2+ and Ba2+) or potentiated the inhibition caused by Ca2+-deprived medium (Mn2+ and Co2+). ATP and creatine phosphate contents were similar in nerves incubated in Ca2+-deprived medium and in Ca2+-containing Ringer's. Thus, inhibition of AXT in the former situation was not due to a decreased availability of high energy phosphates. Two calcium antagonists, D-600 and nifedipin, which are potent smooth muscle relaxants, effectively blocked AXT. The present ressults suggest that Ca2+ is specifically required to maintain AXT and that an anlogy exists between Ca2+ regulation during smooth muscle contraction and AXT.
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