[Peroxidative vulnerability of synaptosomal high affinity Ca++-ATPase and pharmacologic effects].
The high affinity Ca++-ATPase participates essentially in the regulation of intrasynaptosomal calcium homeostasis. Related to posthypoxically restricted transmitter release, we examined the influence of newly-generated free radicals (ascorbic acid-ferric salt mixture) or sodium dodecyl sulfate in vitro and of a mild hypobaric hypoxia in vivo on the activity of synaptosomal high affinity Ca++-ATPase. Moreover we tested the effectiveness of piracetam, meclofenoxate hydrochloride, pyritinol and verapamil on the changed enzyme activity subsequent to a hypoxic exposure. The activity of synaptosomal high affinity Ca++-ATPase (1.04 +/- 0.03 mumol Pi/mg.h) is reduced by not more than 40% depending on the concentration of the ascorbic acid-ferric salt mixture used but is nearly totally inhibited by sodium dodecyl sulfate (0.2 mg/ml). Hypobaric hypoxia (18 h, 8.7 kPa) decreases the enzyme activity to 0.79 +/- 0.03 mumol Pi/mg.h. Piracetam, meclofenoxate hydrochloride and pyritinol are protectively effective on the decrease of enzyme activity induced by hypoxia. The results emphasize the importance of intact protein-phospholipid interactions for the enzyme activity and support relations between synaptosomal high affinity Ca++-ATPase and transmitter release.
Blaschke
M
M
Institut für Pharmakologie und Toxikologie, Medizinische Akademie, Dresden, DDR.
Fischer
H D
HD
Schmidt
J
J
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D005609:Free Radicals; D006706:Homeostasis; D008297:Male; D002504:Meclofenoxate / Q000494:pharmacology; D010889:Piracetam / Q000494:pharmacology; D011746:Pyrithioxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D005609:Free Radicals; D012967:Sodium Dodecyl Sulfate; D011746:Pyrithioxin; D002504:Meclofenoxate; D000252:Calcium-Transporting ATPases; D001205:Ascorbic Acid; D002118:Calcium; D010889:Piracetam
Zur peroxidativen Schädigung der synaptosomalen hochaffinen Ca++-ATPase und ihrer pharmakologischen Beeinflussbarkeit.