Cimetidine transport in isolated brush border membrane vesicles from bovine choroid plexus

Journal Article · Thu Nov 01 04:00:00 EST 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6324473

Whittico, M T; Gang, Y A; Giacomini, K M ^[1]

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1. Univ. of California, San Francisco (USA)

The purpose of this study was to elucidate the mechanisms involved in the transport of cimetidine across the brush border membrane of choroid plexus epithelium. Brush border membrane vesicles were prepared from bovine choroid plexus and the uptake of (3H)cimetidine was studied using the methods of rapid vacuum filtration and scintillation counting. Cimetidine accumulated in the vesicles with time reaching equilibrium within 2 hr. The amount of cimetidine taken up by the vesicles at equilibrium decreased with increasing extravesicular media osmolarity suggesting that cimetidine accumulates in an osmotically reactive intravesicular space. Binding of cimetidine to the membrane was estimated to be less than 18%. Michaelis-Menten studies demonstrated that cimetidine transport involved both a saturable and a nonsaturable component. The Vmax and Km (mean +/- S.E.) were 16.7 +/- 5.9 pmol/sec/mg protein and 58.1 +/- 3.1 microM, respectively, suggesting that cimetidine is transported across the choroid plexus brush border membrane with a lower affinity and a higher capacity than across the renal brush border membrane. The organic cation, quinidine (0.1 mM), and the amino acid, histidine (20 mM), both significantly reduced the initial, but not the equilibrium, uptake of cimetidine. However, high concentrations (5 mM) of more polar organic cations including tetraethylammonium, as well as of several organic anions including salicylate did not inhibit cimetidine transport. Studies with unlabeled cimetidine revealed a countertransport phenomenon. Attempts to drive the concentrative uptake of cimetidine with various ion gradients were unsuccessful. Of note was the fact that an outwardly directed proton gradient could significantly accelerate the uptake of cimetidine.

• OSTI ID: 6324473
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 255:2; ISSN JPETA; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
AMINO ACIDS
ANIMALS
ATP-ASE
AZOLES
BODY
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CATIONS
CATTLE
CELL CONSTITUENTS
CELL MEMBRANES
CHARGED PARTICLES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
GUANIDINES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HISTIDINE
HYDROGEN COMPOUNDS
HYDROLASES
IMIDAZOLES
INHIBITION
IONS
ISOTOPE APPLICATIONS
KIDNEYS
MAMMALS
MEMBRANE TRANSPORT
MEMBRANES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHOSPHOHYDROLASES
RUMINANTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES