Duodenal phytohaemagglutinin (red kidney bean lectin) stimulates gallbladder contraction in humans

Abstract

Lectins, carbohydrate-specific proteins without enzymatic activity on the ligand, are daily ingested plant proteins which survive the passage through the gastrointestinal tract in a biologically active form. Their binding to glycan determinants of natural glycoconjugates can trigger biological effects. The lectin phytohaemagglutinin (PHA) is abundantly present in red kidney beans and induces cholecystokinin (CCK) release in rats. The aim of the study was to investigate the effect of intraduodenal administration of PHA on plasma CCK levels and gallbladder contraction in humans and to elucidate potential mechanisms of action. Five healthy volunteers underwent four studies. After a basal intraduodenal saline infusion for 30 min, PHA or heat-inactivated PHA was infused in increasing doses: 150 microg, 1.5 mg and 15 mg for 30 min each. Intravenous saline, CCK(1) receptor antagonist dexloxiglumide or atropine were administered in random order. Gallbladder volumes were measured by ultrasonography and plasma CCK levels by radioimmunoassay. Intraduodenal PHA induced gallbladder contraction in a dose-dependent fashion starting with the lowest dose. The highest dose reduced the gallbladder volume to 65.3 +/- 9.4% of basal volume (P < 0.001) whereas heat-inactivated PHA did not have any effect. Blocking CCK(1) or muscarinic receptors completely abolished PHA-stimulated gallbladder contraction (dexloxiglumide 208.7 +/- 23.7%; atropine 104 +/- 7.0% of basal volume) while none of the treatments affected CCK levels. Duodenal administration of PHA potently stimulates gallbladder contraction in humans. This contraction is mediated via cholinergic pathway.