EurekaMag.com logo
+ Site Statistics
References:
53,214,146
Abstracts:
29,074,682
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Simultaneous and independent vs. antagonistic inhibition of muscle carbonic anhydrase iii by acetazolamide and cyanate






Biochemical Pharmacology 33(16): 2641-2646

Simultaneous and independent vs. antagonistic inhibition of muscle carbonic anhydrase iii by acetazolamide and cyanate

The inhibition by cyanate and acetazolamide of pig muscle carbonic anhydrase III (CA III) CO2 hydratase activity was studied in order to explore mechanistic features possibly unique to the muscle isoenzyme. The turnover number of CO2 hydration was found to be 6000 s-1 with a Km of 83 mM for CO2. Cyanate inhibition (Ki, 3 .mu.M) and acetazolamide inhibition (Ki, 44 .mu.M) were both found to be noncompetitive with respect to CO2. Significantly, acetazolamid and cyanate displayed non-exclusive binding to pig muscle carbonic anhydrase. The similarity of mode and degree of inhibition of muscle carbonic anhydrase by cyanate as compared with the inhibition of the erythrocyte isoenzymes suggests the existence of a similar metal environment. That cyanate and acetazolamide bind simultaneously to CA III and the comparatively large Ki for acetazolamide per se appear to be more compatible with a different mode of coordination of the Zn with the sulfonamide, supporting a 5-coordinant Zn in the catalytic mechanism of CO2 hydration for CA III.

(PDF 0-2 workdays service: $29.90)

Accession: 006418987



Related references

Simultaneous and independent versus antagonistic inhibition of muscle carbonic anhydrase (CA III) by acetazolamide and cyanate. Biochemical Pharmacology 33(16): 2641-2645, 1984

Inhibition of hypoxia-induced calcium responses in pulmonary arterial smooth muscle by acetazolamide is independent of carbonic anhydrase inhibition. American Journal of Physiology. Lung Cellular and Molecular Physiology 292(4): L1002-L1012, 2007

Specific inhibition of kidney carbonic anhydrase in a histological section by means of 2-acetylamino-1, 3, 4-thiadiazole-5-sulfonamide; simultaneous contribution to the histopography of carbonic anhydrase in kidney tissue. Acta Histochemica 2(1-2): 39-46, 1955

Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action. International Journal of Clinical Pharmacology and Therapeutics 39(6): 265-270, 2001

Localization of carbonic anhydrase in living osteoclasts with bodipy 558/568-modified acetazolamide, a thiadiazole carbonic anhydrase inhibitor. Journal of Histochemistry and Cytochemistry 47(4): 545-550, 1999

Effect of secretin gastro intest and acetazolamide carbonic anhydrase inhib on the volume and electrolyte composition of hepatic bile in man enz carbonic anhydrase. Gastroenterology 56(2): 286-294, 1969

Nature of the inhibition of carbonic anhydrase by acetazolamide. FED PROC 19(1 Pt 1): 50, 1960

Carbonic anhydrase and inhibition of gastric secretion by acetazolamide. Medicina Interna 25(10): 1243-1252, 1973

Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. Journal of Pharmacology and Experimental Therapeutics 131: 271-274, 1961

The inhibition of carbonic anhydrase and of gastric acid secretion by thio-cyanate. Amer Jour Physiol 129(3): 505-514, 1940