Inhibition of membrane transport ATPases by halenaquinol, a natural cardioactive pentacyclic hydroquinone from the sponge Petrosia seriata.
Halenaquinol, a natural cardioactive pentacyclic hydroquinone from the sponge Petrosia seriata, was found to be a powerful inhibitor of the rat brainstem and of the rat brain cortex Na+, K(+)-ATPases and the rabbit muscle sarcoplasmic reticulum Ca(2+)-ATPase with I50 values of 7.0 x 10(-7), 1.3 x 10(-6) and 2.5 x 10(-6) M, respectively. Halenaquinol also inhibited K(+)-phosphatase activity of the rat brain cortex Na+, K(+)-ATPase with an I50 value of 3 x 10(-6) M. Ouabain-insensitive Mg(2+)-ATPase activity of the microsomal fraction of the rat brain cortex was weakly inhibited by halenaquinol. Inhibition was irreversible, dose- and time-dependent. Naphthohydroquinone fragment in structures of halenaquinol, related natural and model compounds was very important for an inhibiting effect.
Gorshkova
I A
IA
Pacific Institute of Bioorganic Chemistry, Far East Division of the Russian Academy of Sciences, Vladivostok, Russia. kav@piboc.marine.su
Gorshkov
B A
BA
Fedoreev
S A
SA
Shestak
O P
OP
Novikov
V L
VL
Stonik
V A
VA
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000737:chemistry* / Q000494:pharmacology*; D001933:Brain Stem / Q000201:enzymology; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011161:Porifera / Q000737:chemistry*; D011817:Rabbits; D011895:Rana ridibunda; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D004791:Enzyme Inhibitors; C074982:halenaquinol sulfate; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase