In vitro and in vivo effects of dantrolene on carbonic anhydrase enzyme activities.
The effects of dantrolene were investigated on carbonic anhydrase (CA) enzyme activities in in vitro human and in in vivo Sprague-Dawley rat erythrocytes. For in vitro study, human carbonic anhydrase-I (HCA-I) and -II (HCA-II) were purified by Sepharose 4B-L-tyrosine-sulfanylamide affinity chromatography, rats were used for in vivo study. In vivo and in vitro CA enzyme activity was determined colorimetrically using the CO(2)-hydration method of Wilbur and Anderson. Dantrolene (1.64 x 10(-5)-6.56 x 10(-5) M) showed in vitro inhibitory effects on HCA-I and HCA-II hydratase activity, when determined using the CO(2)-hydratase method. 50% inhibitory concentration (IC(50)) was 4.09 x 10(-5) M for HCA-I and 3.24 x 10(-5) M for HCA-II. Rat erythrocyte CA activity was significantly inhibited by 10 mg/kg dantrolene for up to 3 h (p<0.001) following intraperitoneal administration. In conclusion, Dantrolene inhibited the carbonic anhydrase enzyme activity under in vitro and in vivo conditions.
Gülçin
Ilhami
I
Atatürk University, Science and Arts Faculty, Department of Chemistry, Turkey. igulcin@atauni.edu.tr
Beydemir
Sükrü
S
Büyükokuroğlu
Mehmet Emin
ME
D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D002256:Carbonic Anhydrases; D003620:Dantrolene