Renal and cerebrospinal fluid formation pharmacology of a high molecular weight carbonic anhydrase inhibitor.
نویسندگان
چکیده
To achieve selective inhibition of cytosolic and membrane-bound carbonic anhydrase (CA II and CA IV, respectively), we synthesized a polymer of molecular weight 3500 from polyoxyethylene bis acetic acid and aminobenzolamide. The new compound, designated F (for Florida) 3500, is stable, water soluble and nontoxic. It is excreted largely unchanged by glomerular filtration. The Ki at 37 degrees C against CA II is 0.14 microM and against CA IV 4.0 microM, some 20 times more than the parent aminobenzolamide and about three times more than acetazolamide or methazolamide. F 3500 does not penetrate red cells and is confined to extracellular fluid. Relations of dose to renal HCO3-excretion was studied by i.v. injection into rats. Peak effect was reached with 100 mg/kg, eliciting 40 mM HCO3- in urine; this is taken to be the effect of inhibiting CA IV. This compares to a peak of 103 mM HCO3- after 3 mg/kg aminobenzolamide, which agrees with previous data on other low molecular weight sulfonamides and defines the effect on CA II and CA IV. We conclude that both isozymes are necessary for normal full renal reabsorption of HCO3-. We studied the effect of perfusing F 3500 (100-4000 microM) through the ventriculo-cisternal system of rats on cerebrospinal fluid (CSF) formation. F 3500 was also given intravenously at 100 mg/kg. CSF formation was unaffected. Low MW sulfonamides by either route lowered CSF formation 30 to 50%. It appears either that membrane-bound enzyme (CA IV) is not accessible from the CSF or blood side or that it plays little or no role in CSF formation.
منابع مشابه
Study of Glycation Process of Human Carbonic Anhydrase II and Investigation of Effect of Fasting On Enzyme Activity by Using Spectroscopic Methods
Background: Glycation is the non-enzymatic reaction between the carbonyl groups in sugar and free amino groups in proteins. this reaction leads to changes in structure and functions of proteins. Advanced glycation end products (AGEs) is the final stage in this process, which is highly oxidizing and destructive nature, causing many diabetic complications. Methods: In the present investigation, ...
متن کاملKinetics of complex formation between human carbonic anhydrase B and heterocyclic sulfonamides.
متن کامل
Properties of a carbonic anhydrase inhibitor protein in flounder serum.
The blood serum of the European flounder Platichthys flesus strongly inhibits soluble erythrocytic carbonic anhydrase from the same species. The inhibition is of the uncompetitive type. Hence, the mechanism of the carbonic anhydrase inhibition is different from that of all other known carbonic anhydrase inhibitors. The serum showed no inhibitory effect on carbonic anhydrase from human and bovin...
متن کاملRole of basolateral carbonic anhydrase in proximal tubular fluid and bicarbonate absorption.
Membrane-bound carbonic anhydrase (CA) is critical to renal acidification. The role of CA activity on the basolateral membrane of the proximal tubule has not been defined clearly. To investigate this issue in microperfused rabbit proximal straight tubules in vitro, we measured fluid and HCO(3)(-) absorption and cell pH before and after the extracellular CA inhibitor p-fluorobenzyl-aminobenzolam...
متن کاملSynthesis and Evaluation of Antimicrobial Activity of Metal Complexes of 4-(2'-Hydroxy Phenyl Imino) Phenyl Sulphonamide
Keeping in view the promising potential of carbonic anhydrase inhibitor based antimicrobials and enhancement of carbonic anhydrase inhibitory activity by metal complexes of sulfonamides, with an aim to develop better antimicrobial agents we have attempted investigation of antimicrobial activity of metal complexes of 4-(2'-hydroxy phenyl imino) phenyl sulphonamide. Sulfanilamide was taken...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 280 1 شماره
صفحات -
تاریخ انتشار 1997