Effect of P-glycoprotein modulators on alkaline phosphatase activity in cultured rat hepatocytes

• Type: Article in International Scientific Journal
• Date: 2000

Authors

Conceicao Calhau (Author) FCNAUP; Martel, F (Author) FMUP; Hipolito Reis, C (Author) Other; Azevedo, I (Author) Other

Journal

Title: Cellular Physiology and Biochemistry

Vol. 10

Pages: 195-202

ISSN: 1015-8987

Publisher: Cell Physiol Biochem Press

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 23 Citations

Other information

Authenticus ID: P-001-18K

DOI: 10.1159/000016350

Abstract (EN): Alkaline phosphatases (orthophosphoric-monoester phosphohydrolase, E.C. 3.1.3.1) are a group of nonspecific phosphomonoesterases located primarily in the plasma membrane of the cells in which they occur [1]. It was recently demonstrated that alkaline phosphatase (ALP) concentration in different tissues is positively correlated with the extent of exchange surface per unit volume of the tissue, suggesting an association between ALP and transport systems [2]. Moreover, several groups [3,4,5] obtained evidence of an involvement of ALP in the modulation of P-glycoprotein activity in hepatocytes. The aim of the present study was to determine the putative influence of compounds known to modulate P-glycoprotein-mediated transport on hepatic ALP activity, by using primary cultured rat hepatocytes. The K-m and V-max values of ALP were determined (657.2 muM (306.8-933.1) and 32.0+/-1.5 nmol mg protein(-1) min-respectively). Vanadate and corticosterone concentration-dependently reduced ALP activity, producing maximal reductions of 79% (100 muM) and 71% (100 muM), respectively. The IC50's were found to be 7.9 muM (2.1-29.5 muM) and 2.4 muM (0.2-35.2 muM), respectively. Cyclosporin A, verapamil, octreotide, kaempferol, daunomycin and genistein produced a concentration-dependent increase in ALP activity. ALP activity was maximally increased to 253%, 390%, 180%, 487%, 449% and 193% of control in the presence of 100 muM cyclosporin A, 50 muM verapamil, 10 muM octreotide, 100 muM kaempferol, 100 muM daunomycin and 1 muM genistein, respectively. The results show that all P-glycoprotein modulators tested were able to significantly affect the activity of hepatic-ALP. These effects on ALP activity may contribute to the modulation of P-glycoprotein activity by these drugs. Copyright (C) 2000 S. Karger AG, Basel.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8