The mode of inhibitory action of alpha-mangostin, a novel inhibitor, on the sarcoplasmic reticulum Ca(2+)-pumping ATPase from rabbit skeletal muscle.
alpha-Mangostin, the principal ingredient of the fruit hull of Garcinia mangostana, caused a concentration-dependent decrease in the activities of both Ca(2+)-ATPase and Ca(2+)-transport of the sarcoplasmic reticulum from rabbit skeletal muscle with an IC50 value of 5 microM. Neither Ca2+ release nor other enzyme activities were affected by alpha-mangostin. Kinetic analysis of the inhibitory effects of alpha-mangostin on Ca(2+)-ATPase suggests that the inhibition of the ATPase is a noncompetitive-type with respect to ATP or Ca2+. alpha-Mangostin may become a useful pharmacological tool for clarifying the physiological functions of Ca(2+)-pumping ATPase and sarcoplasmic reticulum.
Furukawa
K
K
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Shibusawa
K
K
Chairungsrilerd
N
N
Ohta
T
T
Nozoe
S
S
Ohizumi
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018482:Muscle, Skeletal / Q000187:drug effects*; D011494:Protein Kinases / Q000494:pharmacology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D014966:Xanthenes; D044004:Xanthones; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D002118:Calcium; C021053:mangostin