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.


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.
Martins
M J
MJ
Department of Biochemistry, Faculty of Medicine (U38-FCT), University of Porto, 4200-319 Porto, Portugal. mmartins@med.up.pt
Negrão
M R
MR
Hipólito-Reis
C
C
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004791:Enzyme Inhibitors; D013656:Taurocholic Acid; D000469:Alkaline Phosphatase