Kinetics and mechanism of in vitro uptake of amino-β-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system

Nakashima Emi, Tsuji Akira, Mizuo Hitoshi, Yamana Tsukinaka

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

By utilizing the everted jejunum of rats, the initial uptake rates of several antibiotics were measured over a wide range of concentrations. The uptakes followed mixed-type kinetics involving saturable and non-saturable processes in parallel. The pertinent kinetic parameters for the uptake of each antibiotic were determined. The effect of cephalexin on the uptake of cyclacillin obeyed competitive inhibition kinetics, and the inhibition constant Ki was found to be equal to the Michaelis constant Ki for the uptake of cephalexin itself. In a similar way, the uptake of cephalexin was inhibited by cyclacillin. Uptakes of both cyclacillin and cephalexin were reduced significantly by several metabolic inhibitors. From the effect of temperature on the uptakes of cyclacillin and cephalexin, activation energies of 24.8 and 23.1 kcal/mole were obtained respectively. These results indicate the involvement of an active transport mechanism for cyclacillin and cephalexin. It was found that several dipeptides markedly inhibited the uptakes of cyclacillin and cefadroxil. Furthermore, the uptake of glycylglycine, a typical dipeptide, was inhibited by cyclacillin, cefadroxil, cephalexin, and cephradine. The kinetics of mutual inhibition of the uptakes of cyclacillin and glycylglycine were consistent with competitive-type inhibition. This is the first report which establishes, from a kinetic point of view, the involvement of a common transport system in the in vitro uptakes of the dipeptides and the antibiotics.

Original languageEnglish
Pages (from-to)3345-3352
Number of pages8
JournalBiochemical Pharmacology
Volume33
Issue number21
DOIs
Publication statusPublished - 1984 Nov 1
Externally publishedYes

Fingerprint

Cyclacillin
Lactams
Cephalexin
Small Intestine
Rats
Anti-Bacterial Agents
Kinetics
Dipeptides
Cefadroxil
Glycylglycine
Cephradine
peptide permease
In Vitro Techniques
Active Biological Transport
Jejunum
Kinetic parameters
Activation energy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Kinetics and mechanism of in vitro uptake of amino-β-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system. / Emi, Nakashima; Akira, Tsuji; Hitoshi, Mizuo; Tsukinaka, Yamana.

In: Biochemical Pharmacology, Vol. 33, No. 21, 01.11.1984, p. 3345-3352.

Research output: Contribution to journalArticle

Emi, Nakashima ; Akira, Tsuji ; Hitoshi, Mizuo ; Tsukinaka, Yamana. / Kinetics and mechanism of in vitro uptake of amino-β-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system. In: Biochemical Pharmacology. 1984 ; Vol. 33, No. 21. pp. 3345-3352.
@article{907f6e0b693040ea9107312a06844200,
title = "Kinetics and mechanism of in vitro uptake of amino-β-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system",
abstract = "By utilizing the everted jejunum of rats, the initial uptake rates of several antibiotics were measured over a wide range of concentrations. The uptakes followed mixed-type kinetics involving saturable and non-saturable processes in parallel. The pertinent kinetic parameters for the uptake of each antibiotic were determined. The effect of cephalexin on the uptake of cyclacillin obeyed competitive inhibition kinetics, and the inhibition constant Ki was found to be equal to the Michaelis constant Ki for the uptake of cephalexin itself. In a similar way, the uptake of cephalexin was inhibited by cyclacillin. Uptakes of both cyclacillin and cephalexin were reduced significantly by several metabolic inhibitors. From the effect of temperature on the uptakes of cyclacillin and cephalexin, activation energies of 24.8 and 23.1 kcal/mole were obtained respectively. These results indicate the involvement of an active transport mechanism for cyclacillin and cephalexin. It was found that several dipeptides markedly inhibited the uptakes of cyclacillin and cefadroxil. Furthermore, the uptake of glycylglycine, a typical dipeptide, was inhibited by cyclacillin, cefadroxil, cephalexin, and cephradine. The kinetics of mutual inhibition of the uptakes of cyclacillin and glycylglycine were consistent with competitive-type inhibition. This is the first report which establishes, from a kinetic point of view, the involvement of a common transport system in the in vitro uptakes of the dipeptides and the antibiotics.",
author = "Nakashima Emi and Tsuji Akira and Mizuo Hitoshi and Yamana Tsukinaka",
year = "1984",
month = "11",
day = "1",
doi = "10.1016/0006-2952(84)90104-7",
language = "English",
volume = "33",
pages = "3345--3352",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "21",

}

TY - JOUR

T1 - Kinetics and mechanism of in vitro uptake of amino-β-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system

AU - Emi, Nakashima

AU - Akira, Tsuji

AU - Hitoshi, Mizuo

AU - Tsukinaka, Yamana

PY - 1984/11/1

Y1 - 1984/11/1

N2 - By utilizing the everted jejunum of rats, the initial uptake rates of several antibiotics were measured over a wide range of concentrations. The uptakes followed mixed-type kinetics involving saturable and non-saturable processes in parallel. The pertinent kinetic parameters for the uptake of each antibiotic were determined. The effect of cephalexin on the uptake of cyclacillin obeyed competitive inhibition kinetics, and the inhibition constant Ki was found to be equal to the Michaelis constant Ki for the uptake of cephalexin itself. In a similar way, the uptake of cephalexin was inhibited by cyclacillin. Uptakes of both cyclacillin and cephalexin were reduced significantly by several metabolic inhibitors. From the effect of temperature on the uptakes of cyclacillin and cephalexin, activation energies of 24.8 and 23.1 kcal/mole were obtained respectively. These results indicate the involvement of an active transport mechanism for cyclacillin and cephalexin. It was found that several dipeptides markedly inhibited the uptakes of cyclacillin and cefadroxil. Furthermore, the uptake of glycylglycine, a typical dipeptide, was inhibited by cyclacillin, cefadroxil, cephalexin, and cephradine. The kinetics of mutual inhibition of the uptakes of cyclacillin and glycylglycine were consistent with competitive-type inhibition. This is the first report which establishes, from a kinetic point of view, the involvement of a common transport system in the in vitro uptakes of the dipeptides and the antibiotics.

AB - By utilizing the everted jejunum of rats, the initial uptake rates of several antibiotics were measured over a wide range of concentrations. The uptakes followed mixed-type kinetics involving saturable and non-saturable processes in parallel. The pertinent kinetic parameters for the uptake of each antibiotic were determined. The effect of cephalexin on the uptake of cyclacillin obeyed competitive inhibition kinetics, and the inhibition constant Ki was found to be equal to the Michaelis constant Ki for the uptake of cephalexin itself. In a similar way, the uptake of cephalexin was inhibited by cyclacillin. Uptakes of both cyclacillin and cephalexin were reduced significantly by several metabolic inhibitors. From the effect of temperature on the uptakes of cyclacillin and cephalexin, activation energies of 24.8 and 23.1 kcal/mole were obtained respectively. These results indicate the involvement of an active transport mechanism for cyclacillin and cephalexin. It was found that several dipeptides markedly inhibited the uptakes of cyclacillin and cefadroxil. Furthermore, the uptake of glycylglycine, a typical dipeptide, was inhibited by cyclacillin, cefadroxil, cephalexin, and cephradine. The kinetics of mutual inhibition of the uptakes of cyclacillin and glycylglycine were consistent with competitive-type inhibition. This is the first report which establishes, from a kinetic point of view, the involvement of a common transport system in the in vitro uptakes of the dipeptides and the antibiotics.

UR - http://www.scopus.com/inward/record.url?scp=0021645842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021645842&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(84)90104-7

DO - 10.1016/0006-2952(84)90104-7

M3 - Article

C2 - 6497897

AN - SCOPUS:0021645842

VL - 33

SP - 3345

EP - 3352

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 21

ER -