Inhibition of tRNA aminoacylation by amphetamines

reversal by polyamines

Thaddeus Nowak, H. N. Munro

Research output: Contribution to journalArticle

Abstract

Amphetamines inhibit in vitro protein synthesis in reticulocyte cell-free systems, and in parallel inhibit aminoacylation of tRNAs for several amino acids (T.S. Nowak, Jr. and H.N. Munro, (1977). Except for phenylalanyl tRNA synthetase, which shows competition between phenylalanine and various amphetamines (D.V. Santi and P.V. Danneberg, Biochemistry (1971), pyrophosphate exchange reactions are unaffected. The inhibitory effect of 5 mM parachloroamphetamine (pCA) on charging of reticulocyte tRNA with leucine can be prevented by addition of equimolar spermine. A comparable degree of aminoacylation inhibition was obtained with 100 μM ethidium bromide, and was also reversed by spermine, suggesting a similarity in these actions of ethidium and pCA. Ethidium at much lower concentration (1 μM) is known to bind with high affinity to a few sites on tRNAs, with formation of a fluorescent ethidium - tRNA complex. Spermine (1 mM) eliminated this fluorescent interaction between reticulocyte tRNA and ethidium (1 μM), while up to 20 mM pCA had no effect on the fluorescence. Thus pCA apparently does not interact with the small number of high-affinity fluorescent ethidium binding sites on tRNAs. Polyamines presumably act at other sites on tRNAs or synthetases to prevent the inhibitory effects of amphetamines on aminoacylation.

Original languageEnglish (US)
JournalFederation Proceedings
Volume37
Issue number6
StatePublished - Jan 1 1978
Externally publishedYes

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Transfer RNA Aminoacylation
Amphetamines
Ethidium
Polyamines
p-Chloroamphetamine
Transfer RNA
Aminoacylation
Spermine
Reticulocytes
Amino Acid-Specific Transfer RNA
Phenylalanine-tRNA Ligase
Amino Acyl-tRNA Synthetases
Cell-Free System
Phenylalanine
Leucine
Biochemistry
Fluorescence
Binding Sites

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Inhibition of tRNA aminoacylation by amphetamines : reversal by polyamines. / Nowak, Thaddeus; Munro, H. N.

In: Federation Proceedings, Vol. 37, No. 6, 01.01.1978.

Research output: Contribution to journalArticle

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