The influence of the 1,4-dihydropyridines (DHPs), water-soluble
glutapyrone available as
sodium,
potassium and
ammonium salts of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-DHP-4-carboxamide)glutaric
acid, from one side, and a lipophylic
cerebrocrast, 2-propoxyethyl 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-DHP-3,5-dicarboxylate, from the other side, on partially damaged mitochondria of the Wistar rat hindlimb muscle was also studied. The following tests were made: (1) rates of endogenous respiration and substrate (
succinate) oxidation and oxidative phosphorylation; (2) rates and amplitudes of high-amplitude swelling and contraction after the addition of
ATP,
ADP and
succinate to the previously swollen mitochondria and (3) rate of reversible self-aggregation of mitochondria isolated in
salt media after
ATP-induced contraction without and in the presence of
azidothymidine (AZT).
Cerebrocrast (10-100 microM) partially normalized the endogenous respiration rate and slightly augmented the respiration rate after the addition of
succinate and to lesser extent
ADP.
Cerebrocrast in a concentration-dependent manner (2.5-50 microM) increased (two-fold at 20-50 microM) the active contraction amplitude of swollen mitochondria, induced by single or repeated additions of
ATP. The influence of
cerebrocrast on the
ADP- and
succinate-induced contractions was less obvious. Unlike
cerebrocrast glutapyrone caused a reduction of the
ATP-induced contraction amplitude (two-fold at 0.5-5.0 mM), not impairing the mitochondrial contraction ability in response to
ATP or
succinate. Pre-exposure to 2.5 mM
glutapyrone resulted in at least a 10-fold inhibition of the reversible aggregation rate in the presence of 99 and 198 microM AZT. The results suggest the usefulness of further study of
cerebrocrast and
glutapyrone in preventing AZT-induced and some other
mitochondrial myopathies.