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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Duodenal administration of PHA potently stimulates gallbladder contraction in humans. This contraction is mediated via cholinergic pathway.
Purhonen
A K
AK
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, Kuopio University Hospital, University of Kuopio, Kuopio, Finland.
Herzig
K H
KH
Gabius
H J
HJ
André
S
S
Ketterer
S
S
Matzinger
D
D
Beglinger
C
C
Hildebrand
P
P
D000328:Adult; D001285:Atropine / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood / Q000502:physiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004386:Duodenum; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D016473:Gallbladder Emptying / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010421:Pentanoic Acids / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D016037:Single-Blind Method; D014463:Ultrasonography
D018727:Muscarinic Antagonists; D010421:Pentanoic Acids; D010835:Phytohemagglutinins; D011949:Receptors, Cholecystokinin; D011976:Receptors, Muscarinic; C103490:dexloxiglumide; D001285:Atropine; D002766:Cholecystokinin