Intestinal transport of 3H-digitoxin in vitro incompatible with simple diffusion.
On everted jejunal segments of mice the transfer and tissue uptake of 3H-digitoxin, over a concentration range from 2 times 10(-10)--1 times 10(-4)M, was investigated from the mucosal ("m") to the serosal ("s") side as well as in the opposite direction. 1. The time course of the absorption of 3H-digitoxin and some other compounds investigated (glucose, urea, p-aminohippurate) gave evidence of functional integrity throughout the 75 min-periods of the experiments. 2. When 3H-digitoxin was applied to the mucosal side the permeability coefficient showed a dose-dependent increase but returned to lower values at higher concentrations. When 3H-digitoxin was administered to the serosal side the permeability coefficient showed a dose-dependent decrease at high concentrations. The ratio of both coefficients "m" leads to "s"/"s" leads to "m" increased dose-dependently from 0.4--2.6. 3. The uptake of 3H-digitoxin--applied on the serosal side--into the tissue was independent of dose. However, having administered 3H-digitoxin on the mucosal side the tissue accumulation was 2--5 fold higher and the tissue/medium (T/M) ratio increased within the concentration range from 3.0-9.0 4. Under DNP (1 mM) the asymmetry and dose dependence of the permeability and tissue uptake up 3H-digitoxin observed in controls were almost abolished. Therefore it is likely that the transfer of 3H-digitoxin in the intact intestine involves a mechanism more complex than simple diffusion. The existence of more than a two compartment system and/or the contribution of an active transport mechanism is suggested.
D000618:Aminohippuric Acids / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D004058:Diffusion; D004074:Digitoxin / Q000378:metabolism*; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012704:Serous Membrane / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D014508:Urea / Q000378:metabolism
D000618:Aminohippuric Acids; D004140:Dinitrophenols; D014316:Tritium; D014508:Urea; D004074:Digitoxin; D005947:Glucose