In-vivo inhibition by polycations of small intestinal absorption of methyl alpha-D-glucoside and leucine in the rat.
Polycations are able to inhibit active transport processes in rat small intestine in vitro. Whether this effect can also be confirmed in vivo is the concern of this study. Therefore, the effect of various polycations, e.g., protamine and polylysine, on the absorption of methyl alpha-D-glucoside and leucine was investigated in vivo by single-pass perfusion of rat jejunum. The inhibition of absorption of methyl alpha-D-glucoside and leucine by the polycations was strongly dose dependent. At a substrate concentration of 1 mmol/l a 50% inhibition was achieved with a protamine concentration of 3.2 mg/ml. The inhibition increased as the chain length of the polycation increased. In the presence of protamine the concentration-dependent leucine absorption was reduced at leucine concentrations below 60 mmol/l, but was increased at 100 mmol/l. Absorption of mannitol and 2-deoxy-D-glucose was significantly enhanced by the polycations. These results demonstrate that polycations inhibit active transport and increase passive diffusion processes in the rat small intestine in vivo. In addition, pretreatment of rats with a polycation added to the drinking water impaired the small intestinal absorption of methyl alpha-D-glucoside as subsequently measured by the tissue accumulation technique in vitro. Since polycations are hardly absorbed in the intestine, but do attach to negatively charged groups at the mucosal surface, polycations may be useful to study the influence of these negative groups on the absorption of nutrients and drugs.
Elsenhans
B
B
Walther-Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-Universität, München, Federal Republic of Germany.
Schümann
K
K
D000818:Animals; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D008353:Mannitol / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007930:Leucine; D008353:Mannitol; D008757:Methylglucosides; D008759:Methylglycosides; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers; C027020:methylglucoside