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Common inhibitors of membrane H + ‐transport also inhibit carbonic anhydrase
Author(s) -
Villafuerte Francisco C,
Swietach Pawel,
VaughanJones Richard D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1284
Subject(s) - carbonic anhydrase , chemistry , membrane transport , membrane , acetazolamide , biochemistry , biophysics , enzyme , biology , physiology
Selective pharmacological inhibitors of membrane H + ‐equivalent transport are useful tools for studying pH i regulation. The enzyme carbonic anhydrase (CA) facilitates rapid CO 2 /HCO 3 − interconversion, and may also facilitate membrane H + ‐transport. CA inhibition is commonly achieved with sulphonamides or their derivatives. More recently, some non‐sulphonamides have been reported to inhibit the enzyme. We have investigated effects of dimethylamiloride (DMA), cariporide (selective Na + /H + exchange inhibitors), and DIDS (a stilbene HCO 3 − ‐transport inhibitor) on purified CA II activity, and on total CA activity in rat cardiac ventricular homogenates. CA activity (CO 2 hydration rate) was assayed by following the time‐course of pH change after addition of CO 2 ‐saturated water to a HEPES‐buffered solution (pH 8.0, 2°C), containing either CA II, or cardiac CA‐homogenate. DMA had no effect, but cariporide and DIDS were inhibitory. For CA II, the IC 50 values for cariporide and DIDS were 12.4μM and 42μM, respectively. For cardiac CA homogenate, they were 60μM and 316μM. Thus two commonly used H + ‐transport inhibitors also inhibit CA. Some inhibition of H + ‐transport by these drugs may therefore be secondary to inhibition of CA. Supported by the BHF and Wellcome Trust (UK).