title: Profile of P-glycoprotein distribution in the rat and its possible influence on the salbutamol intestinal absorption process.
abstract: The 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 (k(a), 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" k(a) 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.
authors.affiliation: Department of Pharmacy and Pharmaceutics Technology, Faculty of Pharmacy, University of Valencia, Avd. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Valenzuela
authors.forename: Amparo
authors.initials: A
authors.lastname: Nácher
authors.forename: Purificación
authors.initials: P
authors.lastname: Ruiz-Carretero
authors.forename: Adela
authors.initials: A
authors.lastname: Martín-Villodre
authors.forename: Gracia
authors.initials: G
authors.lastname: López-Carballo
authors.forename: Domingo
authors.initials: D
authors.lastname: Barettino
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000378:metabolism*; D000420:Albuterol / Q000032:analysis* / Q000378:metabolism*; D000818:Animals; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000420:Albuterol