MODIFICATION OF SWELLING-CONTRACTION-AGGREGATION PROCESSES IN RAT MUSCLE MITOCHONDRIA BY THE 1,4-DIHYDROPYRIDINES, CEREBROCRAST AND GLUTAPYRONE, THEMSELVES AND IN THE PRESENCE OF AZIDOTHYMIDINE
A. Velena et al., MODIFICATION OF SWELLING-CONTRACTION-AGGREGATION PROCESSES IN RAT MUSCLE MITOCHONDRIA BY THE 1,4-DIHYDROPYRIDINES, CEREBROCRAST AND GLUTAPYRONE, THEMSELVES AND IN THE PRESENCE OF AZIDOTHYMIDINE, Cell biochemistry and function, 15(3), 1997, pp. 211-220
The influence of the 1,4-dihydropyridines (DHPs), water-soluble glutap
yrone available as sodium, potassium and ammonium salts of ,5-diethoxy
carbonyl-1,4-DHP-4-carboxamide)glutaric acid, from one side, and a lip
ophylic cerebrocrast, 2-propoxyethyl -difluoromethoxyphenyl)-1,4-DHP-3
,5-dicarboxylate, from the other side, on partially damaged mitochondr
ia of the Wistar rat hindlimb muscle was also studied. The following t
ests were made: (1) rates of endogenous respiration and substrate (suc
cinate) oxidation and oxidative phosphorylation; (2) rates and amplitu
des of high-amplitude swelling and contraction after the addition of A
TP, ADP and succinate to the previously swollen mitochondria and (3) r
ate of reversible self-aggregation of mitochondria isolated in salt me
dia after ATP-induced contraction without and in the presence of azido
thymidine (AZT). Cerebrocrast (10-100 mu M) partially normalized the e
ndogenous respiration rate and slightly augmented the respiration rate
after the addition of succinate and to lesser extent ADP. Cerebrocras
t in a concentration-dependent manner (2.5-50 mu M) increased (two-fol
d at 20-50 mu M) the active contraction amplitude of swollen mitochond
ria, induced by single or repeated additions of ATP. The influence of
cerebrocrast on the ADP-and succinate-induced contractions was less ob
vious. Unlike cerebrocrast glutapyrone caused a reduction of the ATP-i
nduced contraction amplitude (two-fold at 0.5-5.0 mM), not impairing t
he mitochondrial contraction ability in response to ATP or succinate.
Pre-exposure to 2.5 mM glutapyrone resulted in at least a 10-fold inhi
bition of the reversible aggregation rate in the presence of 99 and 19
8 mu M AZT. The results suggest the usefulness of further study of cer
ebrocrast and glutapyrone in preventing AZT-induced and some other mit
ochondrial myopathies. (C) 1997 John Wiley & Sons, Ltd.