Biol. Pharm. Bull. 27(5) 613—616 (2004)

4.2.1.1) is a well-characterized pH regulatory enzyme in most tissues including erythrocytes, and catalyzes reversible hydration of CO2 to HCO3 and H . The only known physiological function of the CA isozymes is to facilitate the interconversion of CO2 and HCO3 , they therefore play key roles in diverse processes, such as physiological pH control and gas balance, calcification, and photosynthesis. Up to now, fourteen different CA isozymes have been described in higher vertebrates. Among CA isozymes are the cytosolic ones (CA I, CA II, CA III, CA VII); CA-I is found together with CA-II in erythrocytes. CA-II is the most widely distributed CA in the eye, kidney, central nervous system (CNS) and inner ear. There are also membrane-bound (CA IV, CA IX, CA XII, CA XIV), mitochondrial (CA V), secretory forms (CA VI) and several acatalytic forms (CA VIII, CA X, CA XI). CA plays an important role in water and ion transport and pH regulation in kidney, eye, CNS, inner ear and other systems. The CA inhibitor acetazolamide is used for diuresis in some disorders. It may be said that CA plays a role in endolymph and cerebrospinal fluid synthesis and pH regulation, due to the beneficial effects of acetazolamide on endolymphatic hydrops or hydrocephalus. The activity of CA isozymes in human erythrocytes has been shown to vary considerably under physiological conditions. Moreover, changes in CA activity have been associated with such metabolic diseases diabetes mellitus and hypertension. The inhibition of its has been shown to impair H secretion into the proximal small intestinal lumen, thereby decreasing bicarbonate resorption. In addition, inhibition of CA leads to decreased acidification of urine, the production of alkaline urine and eventually metabolic acidosis. Hydantoin derivative dantrolene (1-[[[5-(4-nitrophenyl)-2furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt hydrate) is a peripherally acting skeletal muscle relaxant, and is clinically used in the treatment of muscle spasticity, malignant hyperthermia, and neuroleptic malignant syndrome. It depresses excitation–contraction coupling in the muscle fibre by inhibiting calcium release from the sarcoplasmic reticulum. It also shows calcium channel blocker effect in the smooth muscle membrane, antioxidative and cytoprotective properties. Although dantrolene is used in the treatment of muscle spasticity, malignant hyperthermia, and neuroleptic malignant syndrome, its impact on carbonic anhydrase (CA) activity has not previously been reported. In the present study, the effects of dantrolene were investigated on carbonic anhydrase enzyme activity in in vitro human and in vivo rat erythrocytes.