Linked Life Data

8996186

Source:http://linkedlifedata.com/resource/pubmed/id/8996186

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-2-10
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
98-104
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Renal and cerebrospinal fluid formation pharmacology of a high molecular weight carbonic anhydrase inhibitor.
pubmed:affiliation
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.