Correlation between structures of organic cations and their binding behaviours to brush border membrane isolated from rat small intestine.

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.