3,5-di-t-butyl-4-hydroxyanisole (DTBHA) activation of rat skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase.
3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) increased in a concentration-dependent manner (calculated pEC(50) = 4.55 +/- 0.18 M) the oxalate-stimulated Ca(2+)-pumping rate of rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Kinetic analysis of this effect suggested that the activation of SR Ca(2+)-ATPase operated by (DTBHA) was of both mixed and non-competitive type with respect to ATP in the range of concentrations 0.1-0.5 mM and above 1 mM, respectively; furthermore, it was independent of the free Ca(2+) concentrations. This indicated that the enzyme activation took place through the acceleration of the enzyme-substrate complex breakdown. Moreover, it appeared that its target site was cyclopiazonic acid sensitive. The uncommon ability of (DTBHA) to upregulate SR Ca(2+) uptake is of interest in view of its possible use for treating pathological conditions characterised by cell Ca(2+) overload as well as genetic disorders where SR Ca(2+) homeostasis is altered.
Fusi
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F
Istituto di Scienze Farmacologiche, Università degli Studi di Siena, via E.S. Piccolomini 170, 53100, Siena, Italy.
Tzankova
V
V
Valoti
M
M
Pessina
F
F
Sgaragli
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002083:Butylated Hydroxyanisole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology
D000975:Antioxidants; D007211:Indoles; D002083:Butylated Hydroxyanisole; C430664:3,5-di-tert-butyl-4-hydroxyanisole; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid