Alkaline phosphatase from rat liver and kidney is differentially modulated

Objective: To investigate the effect of inhibitors of alkaline phosphatase (ALP) and modulators of P-glycoprotein (Pgp), multidrug resistance protein (MRP) and hepatic taurocholate uptake on the activity of tissue-nonspecific ALP (TNALP) in liver and kidney. Design and Results: ALP activity was dete...

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Bibliographic Details
Published in:Clinical biochemistry 2001-09, Vol.34 (6), p.463-468
Main Authors: Martins, Maria J, Negrão, Maria R, Hipólito-Reis, Cândido
Format: Article
Language:English
Subjects:
Alkaline phosphatase
Alkaline Phosphatase - analysis
Alkaline Phosphatase - antagonists & inhibitors
Alkaline Phosphatase - metabolism
Animals
ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
IBMX
Kaempferol
Kidney - chemistry
Kidney - metabolism
Levamisole
Lidocaine
Liver - chemistry
Liver - metabolism
Male
Modulation
Organ Specificity - drug effects
Quinidine
Rats
Rats, Wistar
Taurocholic Acid - pharmacokinetics
Theophylline
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Summary:Objective: To investigate the effect of inhibitors of alkaline phosphatase (ALP) and modulators of P-glycoprotein (Pgp), multidrug resistance protein (MRP) and hepatic taurocholate uptake on the activity of tissue-nonspecific ALP (TNALP) in liver and kidney. Design and Results: ALP activity was determined in rat liver and kidney homogenates. Levamisole had a stronger inhibitory effect on renal TNALP than on the hepatic isoform. 1,3-dimethylxanthine (theophylline) almost abolished renal TNALP activity whereas its effect on hepatic TNALP was less intense. 3-isobutyl-1-methylxanthine (IBMX) and lidocaine produced opposite effects, activating hepatic TNALP and inhibiting the kidney isoform. Quinidine significantly inhibited renal TNALP without affecting hepatic TNALP. Kaempferol activated both liver and kidney isoforms, the effect being more pronounced on hepatic TNALP. Conclusions: a) renal TNALP seems to be more sensitive to inhibition than hepatic TNALP, b) TNALP activity studies should take into account the source of ALP isoform and c) ALP pharmacological manipulation in vivo may produce different and even opposite effects in different tissues/organs.
ISSN:0009-9120
1873-2933
DOI:10.1016/S0009-9120(01)00255-7