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Title

Profile of P-glycoprotein distribution in the rat and its possible influence on the salbutamol intestinal absorption process

AuthorsValenzuela, Belén ; Nácher, Amparo; Ruiz-Carretero, Purificación; Martín-Villodre, Adela; López-Carballo, Gracia; Barettino, Domingo
Keywordssalbutamol
verapamil
intestinal absorption
intestinal secretion
P-glycoprotein (P-gp) expression
bioavailability
mRNA
reverse transcription-polymerase chain reaction (RT-PCR)
Western blot
Issue Date15-Apr-2004
PublisherJapanese Pharmacological Society
CitationJournal of Pharmacological Sciences 93(6):1641-1648 (2004)
AbstractThe intrinsic absorption of salbutamol in different intestinal segments of the rat was measured and related with the corresponding intestinal P-glycoprotein (P-gp) expression levels. The apparent absorption rate constants (ka, h-1) observed in each fraction by means of the in situ rat gut absorption method after perfusion of a 0.29-mM isotonic solution of salbutamol were used as absorption indexes. In a separate series of studies, a semiquantitative analysis of the mRNA expression of P-gp by means of polymerase chain reaction and Western blot with an antibody raised against the P-gp were also performed. The in situ ka values determined in the different segments (h-1) showed that the absorption is not homogeneous along the intestinal tract, that is, 0.499 ± 0.054 for colon, 0.474 ± 0.052 for the proximal segment, 0.345 ± 0.014 for the mean, and 0.330 ± 0.023 for the distal fraction. Addition of verapamil to the perfusion fluid did provide a better absorption of salbutamol in the distal segment. The analysis of the mRNA expression and levels of P-gp showed that the enzyme content in each section of the intestine was inversely related to salbutamol absorption
Description8 pages, 2 figures, 2 tables.--PMID: 15124220 [PubMed]
Publisher version (URL)http://dx.doi.org/10.1002/jps.20071
URIhttp://hdl.handle.net/10261/18438
DOI10.1002/jps.20071
ISSN1347-8613 (Print)
Appears in Collections:(IBV) Artículos
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