Effect of cycloheximide on L-leucine transport by Penicillium chrysogenum: involvement of calcium.
Cycloheximide (actidione) has an immediate inhibitory effect on amino acid transport by nitrogen-starved or carbon-starved mycelium suspended in phosphate buffer. High concentrations of phosphate alone are slightly inhibitory; cycloheximide appears to potentiate the effect of phosphate. Ca(2+) reverses the inhibition of transport caused by phosphate plus cycloheximide. Ca(2+) did not relieve the inhibition of protein synthesis. Cycloheximide promotes a continual uptake of (45)Ca(2+) by the mycelium. The cumulative results suggest that (i) membrane-bound Ca(2+) is involved in amino acid transport, (ii) cycloheximide labilizes the membrane-bound Ca(2+), and (iii) phosphate forms a complex with Ca(2+) making it unavailable for its role in transport. The effect of cycloheximide described above is observed within 1 to 2 min after addition of the antibiotic. This initial inhibition occurs more rapidly with 10(-3) M cycloheximide than with 10(-5) M cycloheximide. However, after a longer preincubation time, a curious inverse relationship between cycloheximide concentration and amino acid transport is observed. The mycelium incubated with 10(-5) M cycloheximide remains strongly inhibited (unless the antibiotic is washed away). The mycelium incubated with 10(-3) M cycloheximide recovers about 40% of the transport activity lost during the rapid initial phase. We have no obvious explanation for the inverse effect.
D002021:Buffers; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002247:Carbon Isotopes; D002951:Citrates / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007930:Leucine / Q000378:metabolism*; D010407:Penicillium / Q000378:metabolism*; D010408:Penicillium chrysogenum / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D013997:Time Factors
D002021:Buffers; D002247:Carbon Isotopes; D002951:Citrates; D010710:Phosphates; D003513:Cycloheximide; D004492:Edetic Acid; D007930:Leucine; D002118:Calcium