Correlation Between Structures of Organic Cations and Their Binding Behaviours to Brush Border Membrane Isolated from Rat Small Intestine

Abstract

We have investigated the correlation between the molecular structures of various organic cations and their binding to rat small intestinal brush border membrane. The binding of small quaternary ammonium compounds such as tetramethylammonium and choline to brush border membrane was not sufficient to inhibit methylchlorpromazine binding. However, lauryltrimethylammonium and cetyltrimethylammonium, both quaternary amines with a long carbon chain, inhibited binding significantly. The inhibition was competitive. When the unbranched hydrocarbon chain of the quaternary amines was extended in steps from C1 (methyl) to C16 (cetyl), the inhibitory effect increased sharply with length from C7 (heptyl) to C16. These results suggest that the size of the hydrophobic part of the molecule is an important factor in binding of quaternary ammonium compounds to the brush border membrane. The structure of the hydrophilic part was another factor. In imipramine-related compounds, the order of binding was N-didesmethylimipramine (primary amine) greater than desipramine (secondary) greater than imipramine (tertiary) greater than methylimipramine (quaternary). However, with the small molecular ethylamine-related compounds, binding properties did not reflect differences in the hydrophilic component. Therefore, the effect of the hydrophilic part may be secondary and may depend on the size of the hydrophobic part. We suggest that organic cations which are amphiphilic can bind to a common binding site on brush border membrane through hydrophobic and/or hydrophilic interactions.

Gastrointestinal absorption of quaternary ammonium compounds correlated to their binding to small intestinal brush border membrane in rat

“…The curve shown in Fig. 1 was very similar to that of inhibitory effects of these QACs on methylchlorpromazine binding (Saitoh et al 1990), and there was a good correlation (r = 0.988) between binding behaviour and inhibitory effect, suggesting the presence of common binding sites on the membrane.…”

“…2-Naphthalenesulphonate in the solution was determined by HPLC. The conditions for HPLC (apparatus and column) were the same as described previously (Saitoh et al 1990). Other conditions were as follows: mobile phase, 0.025 M KH2P04 adjusted to pH 2.5 with phosphoric acid-methanol (55:45); flow rate, 0.5 mL min-I; column temperature, 50"C; detector wavelength, 274 nm; and detector sensitivity, 0.01 -0.04 aufs.…”

“…Protein concentration of membrane suspension was determined according to Lowry et al (1951) with bovine serum albumin as a standard. Methylchlorpromazine was determined as reported previously (Saitoh et al 1990).…”

Influence of enhancers on the absorption and on the pharmacokinetics of cefodizime using in-vitro and in-vivo models

“…It is known that amphiphilic organic surfactants can bind to an unspecific site of the luminal cell membrane via hydrophilic or lipophilic interactions. This binding strength decreases with an increasing in the alkyl chain length (Saitoh et al 1990). The influence of the surfactant on active D-glucose transport has been examined in biological lipid membranes (Brot et al 1986).…”