A structure-relationship study of the uptake of aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles.
The effects of lipophilicity, ion-diffusion potential and membrane surface potential on the uptake of various aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles (BBMV) have been investigated. A valinomycin-induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds, and good correlation was observed between lipophilicity and the amount of diffusion-potential-dependent transport of the diamines. In contrast, because of their much lower lipophilicity, tri- and tetraamine compounds were not affected by the diffusion potential. Tetracaine, which can make the membrane surface potential more positive, inhibited the transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV. These data suggest that the transport mechanism of diamines is similar to that of monoamine compounds in respect to its dependence on ion-diffusion potential and on the membrane surface potential. The extent of the effect of ion-diffusion potential on the rate of transport of the diamines was closely related to the lipophilicity of the diamine. In contrast, only the surface potential contributed to the transport mechanism of lower lipophilic tri- and tetraamine compounds.
Kobayashi
M
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Suruga
S
S
Takeuchi
H
H
Sugawara
M
M
Iseki
K
K
Miyazaki
K
K
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003959:Diamines / Q000737:chemistry / Q000493:pharmacokinetics; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000442:Octanols / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry / Q000493:pharmacokinetics*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013748:Tetracaine / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D000779:Anesthetics, Local; D000900:Anti-Bacterial Agents; D002021:Buffers; D003959:Diamines; D007476:Ionophores; D000442:Octanols; D011073:Polyamines; D013748:Tetracaine; D014634:Valinomycin; D011188:Potassium