Gastroenterology Laboratory, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 ONN, United Kingdom
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ABSTRACT |
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We previously showed that soybean lectin (SBL) releases cholecystokinin (CCK) and have now asked whether other dietary lectins have this effect and if extracellular calcium is involved. Lectins and vehicle were first infused into the duodenum of anesthetized rats. The CCK response to vehicle was 3.1 ± 0.6 pmol/l (P < 0.05 vs. basal). SBL and peanut lectin (PNL) (84 µg/ml) significantly increased plasma CCK concentrations from 2.0 ± 0.4 pmol/l to a maximum of 8.4 ± 0.5 pmol/l (P < 0.01 vs. vehicle, mean ± SE) and from 1.9 ± 0.5 to 7.0 ± 0.6 pmol/l (P < 0.05 vs. vehicle, mean ± SE), respectively. Wheat germ lectin (WGL) (840 µg) also increased plasma CCK levels from 1.5 ± 0.3 pmol/l to a maximum of 9.7 ± 1.3 pmol/l (P < 0.05 vs. vehicle, mean ± SE). Corresponding increases in pancreatic protein output occurred. Broad bean lectin (BBL) had no effect on either parameter. Dose-dependent responses were seen with SBL, PNL, and WGL (1, 10, and 100 µg/ml) in perifused rat intestinal cells. These responses were abolished in calcium-free medium and in the presence of the competing sugars of the lectins. Therefore, SBL, PNL, and WGL, which bind to motifs including N-acetyl-D-galactosamine, galactose, and N-acetylglucosamine, respectively, released CCK, but BBL, which binds to mannose and glucose, did not. Ingestion of lectins may have major CCK-mediated effects on gastrointestinal function and growth.
plant agglutinins; pancreatic juice; trypsin
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INTRODUCTION |
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THE INTESTINAL HORMONE cholecystokinin (CCK) is an important regulator of upper gastrointestinal functions, including gallbladder contraction, pancreatic secretion and growth, gastric emptying, and satiety (20).
Raw soybean flour releases CCK in many species, including humans (5), and diets of raw soybean flour stimulate pancreatic growth in rats (6, 21). This was initially attributed to soybean trypsin inhibitors (SBTI) (9, 21), but Grant et al. (9) showed that ingestion of soybean lectin (SBL) reproduces this effect (9). We (14) showed that depletion of lectin from raw soy flour greatly diminishes its CCK-releasing effect. Pure SBL released CCK, thus stimulating pancreatic enzyme secretion in anesthetized rats, and SBTI acted synergistically with the lectin (14).
A normal diet contains many lectins (24). They are generally heat labile, but considerable amounts remain after cooking (31). Once ingested, lectin activity largely persists during passage through the gastrointestinal tract (4, 16, 31). Therefore, we have now asked whether other lectins release CCK.
Lectins were chosen to represent the groups described by Goldstein and
Poretz (8). This is based on the finding that lectins that bind to
motifs including
N-acetyl-D-galactosamine
tend to stimulate intestinal cells (18, 19, 31). These include soybean (Glycine
max) lectin (SBL), which binds to
N-acetyl-D-galactosamine and D-galactose, and peanut
(Arachis
hypogaea) lectin (PNL), which binds
to
D-galactose--1,3-N-acetyl-D-galactosamine.
The latter stimulates proliferation of colonic cell lines as well as
normal and diseased colonic epithelia (29, 31). In contrast, lectins that bind to mannose or glucose tend to have no effects or even inhibit
processes such as proliferation (13, 19). Broad bean (Vicia
faba) lectin (BBL) is a member of
this group. Wheat germ (Triticum
vulgaris) lectin (WGL) binds to
N-acetyl-D-glucosamine and causes calcium-dependent stimulation of enterocytes (33). This is
interesting because elevations of intracellular calcium can release CCK
(20, 23).
For in vivo studies we used our anesthetized rat model (14) with bile-pancreatic juice returned to the duodenum. The addition of protein cooked soybean flour (CSF) and SBTI increases the sensitivity of this model to lectins. In view of this, we also examined the stability of lectin activity in bile-pancreatic juice. The role of calcium was examined in an in vitro system based on preparations of perifused intestinal cells (3).
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MATERIALS AND METHODS |
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Chemicals, including lectins, were purchased from Sigma (Pole, Dorset, UK) unless otherwise stated.
Effects of Lectins on Pancreatic Protein Output and Plasma CCK Concentrations in Anesthetized Rats
Preparation of animals. The rat model and experimental procedure were as described previously (14). Briefly, male Sprague-Dawley rats (200-300 g) were lightly anesthetized with halothane, and cannulas were placed in the duodenum, bile-pancreatic duct, and jugular vein. The temperature of the rats was maintained at 37°C throughout the experiment.
Experimental procedure. Intraduodenal test infusions were given at least 90 min after surgery to allow pancreatic output to reach a steady state. The amounts of lectins used were chosen on the basis of our previous finding that either 30 mg of raw soybean flour or the 84 µg of lectin that it contains significantly increase CCK release and pancreatic protein output in the rat model (14). We therefore examined the effects of 84 µg of each lectin. If no response was seen, a dose of 840 µg was then used. The lectin was added to 44 mg of CSF and 0.16 mg SBTI at 37°C and infused into the duodenum in a total volume of 0.6 ml over 15 min. Bile-pancreatic juice was collected continuously in 15-min aliquots into tared 1.5-ml Microfuge tubes, and the volume was determined by weight. We retained 20 µl for protein assay. The remainder was kept at 37°C and slowly returned to the duodenum. Test substances CSF, SBTI, and lectin were mixed with bile-pancreatic juice immediately before reinfusion. Blood samples (0.5 ml) were taken from the jugular vein for CCK radioimmunoassay immediately before and every 15 min after the test substance was infused.
Assay of protein and CCK. Protein was measured in bile-pancreatic juice using dye-concentrate solution (Bio-Rad, Hertfordshire, UK) with bovine serum albumin as the standard. Peak pancreatic protein output occurred 30-45 min after the infusion of test substances. One-hour protein responses were calculated as the total protein output during the hour after infusion minus twice that during the 30 min preceding the infusion.
CCK was measured by a specific radioimmunoassay using antibody Dino7, as described previously (14). The concentrations of pure peptides that produced half-maximal inhibition of tracer binding to antiserum Dino7 in this assay are 1.7 pmol/l for CCK-8, 3.2 pmol/l for porcine CCK-33 (Peninsula Laboratories, St. Helen's, UK), 4.8 nmol/l for sulfated gastrin-17, and 5.7 nmol/l for nonsulfated gastrin-17. The detection limit of the assay, defined as the smallest concentration of CCK-8 per assay tube that could be differentiated from the absence of CCK with 95% confidence, was 0.2 pmol/l. The intra- and interassay variabilities of the assay were 6.2% and 12.1%, respectively.Effects of Lectins on CCK Release from Perifused Intestinal Mucosal Cells
Perifused intestinal cell preparation. This method was as described by Bouras et al. (3). Briefly, intestinal cells are prepared by incubating everted proximal small intestine of male Sprague-Dawley rats in calcium-free medium with EDTA. Cell viability as assessed by trypan blue exclusion was >95%. The cells were then mixed with Sephadex G50 beads (Pharmacia, Uppsala, Sweden) and supported on a 5-µm nylon filter in columns made from disposable 3-ml syringes (107-108 cells/column). Cells were equilibrated for 1 h with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer, pH 7.4, at 37°C in a water bath and oxygenated with 100% oxygen. After 1-h equilibration, basal CCK output was measured. Cells were then perifused with 5 ml buffer containing 1, 10, or 100 µg/ml of SBL, PNL, WGL, and BBL. Four 5-min collections were then made. The first was discarded, because the dead space was ~5 ml. The release of CCK (fmol/fraction) was represented as means ± SE of CCK in three 5-min collections from n = 6 experiments determined by radioimmunoassay. CCK peptides were extracted from perfusates using C-18 Sep-Pak cartridges (Waters Millipore), as described by Bouras et al. (3). Sep-Pak eluates were lyophilized directly in the radioimmunoassay tubes before CCK assay as described above.
Role of calcium in lectin-mediated CCK secretion.
To establish whether cellular responses were dependent on extracellular
calcium, we exposed the cells to lectins in a calcium-free medium
containing 2 mM ethylene glycol-bis(-aminoethyl
ether)-N,N,N',N'-tetraacetic acid (EGTA) substituted for CaCl2.
Responses to repeated lectin administration. This was studied to address whether CCK-releasing cells were damaged by exposure to lectin. After initial exposure to the lectins, cells were perfused with HEPES buffer containing the complementary sugar of the lectins (N-acetyl-D-galactosamine for SBL, D-galactose for PNL, N,N',N''-triacetylchitotriose for WGL, and mannose for BBL, all at 10 mM) to elute the lectin. The cells were then perfused with HEPES buffer for 15 min and rechallenged with the same lectin.
Stability of SBL, PNL, WGL, and BBL in Activated Pancreatic Juice
The method was based on that used by Borgstrom et al. (2). Rat bile-pancreatic juice was collected on ice. Samples (1 ml) were mixed with 600 µl of a tris(hydroxymethyl)aminomethane (Tris)-maleate buffer (50 mmol/l, pH 5.6) containing 10 mmol/l CaCl2 and 84 µg lectin at room temperature. The mixture was then activated by adding 400 µg of enterokinase in 400 µl of the above-mentioned buffer, to give a final pH of 7.4. The mixture was incubated for 0, 30, and 60 min at 37°C, then stopped by adding an excess of SBTI. Remaining lectin activity was measured by agglutination of red blood cells at serial dilutions against lectin standards (15). Group O erythrocytes pretreated with papain were used to detect SBL and WGL. Group O erythrocytes treated with neuraminidase were used to detect PNL and BBL.Effect of Lectins on Trypsin Activity
Trypsin activity was measured in the presence and absence of lectins based on hydrolysis of NData Analysis
Results were compared by Student's t-test. P < 0.05 was considered significant. ![]() |
RESULTS |
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Effects of Lectins on Pancreatic Protein Output and CCK Release in Anesthetized Rats
Effects of lectins on pancreatic protein output. The addition of SBTI to CSF produced a modest rise in the 1-h integrated protein response of 0.7 ± 0.2 mg/h (Fig. 1). This was therefore used as the negative control in statistical analysis. The addition of 84 µg SBL to vehicle (CSF plus SBTI) stimulated a 1-h integrated protein response of 2.5 ± 0.7 mg/h (P < 0.05 vs. vehicle). PNL (84 µg) with vehicle stimulated a 1-h integrated protein response of 1.9 ± 0.6 mg/h (P < 0.05 vs. vehicle). WGL (84 µg) had no significant effect, but increasing the dose to 840 µg stimulated a 1-h integrated protein response of 3.3 ± 1.2 mg/h (P < 0.05 vs. vehicle). In contrast, BBL had no significant effect at 84 or 840 µg/ml.
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Effect of lectins on CCK release in anesthetized rats. Plasma CCK concentrations were significantly elevated 3.1 ± 0.6 pmol/l (P < 0.05 vs. basal) by CSF plus SBTI (vehicle) in a volume of 600 µl (Fig. 2). SBL (84 µg) plus vehicle significantly stimulated CCK release to 8.4 ± 0.6 pmol/l (P < 0.05 vs. vehicle). PNL (84 µg) plus vehicle significant increased plasma CCK concentrations to 7.0 ± 0.6 pmol/l (P < 0.05 vs. vehicle). WGL (840 µg) significantly increased CCK release to 9.7 ± 1.3 pmol/l (P < 0.05 vs. vehicle). BBL had no effect on CCK release at 84 or 840 µg, being 2.8 ± 0.7 and 2.6 ± 0.4 pmol/l, respectively.
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Effects of Lectins on CCK Release from Perifused Intestinal Mucosal Cells
Measurement of CCK release from perifused intestinal mucosal cells. HEPES buffer produced a basal CCK output of 1.8 ± 0.4 fmol (Fig. 3). Potassium chloride (50 mM), which was used as the positive control, stimulated a CCK response of 8.5 ± 0.5 fmol (P < 0.01 vs. basal). None of the lectins produced a significant response when used at the lower concentration of 1 µg/ml, but all had a significant effect at 10 and 100 µg/ml; SBL (1, 10, and 100 µg/ml) stimulated a CCK output of 2.0 ± 0.7, 7.9 ± 0.4, and 11.2 ± 1.1 fmol, respectively (10 and 100 µg/ml both P < 0.05 vs. basal). PNL (1, 10, and 100 µg/ml) stimulated a CCK output of 2.2 ± 0.4, 5.7 ± 0.6, and 8.4 ± 1.1 fmol, respectively (10 and 100 µg/ml both P < 0.05 vs. basal), and WGL (1, 10, and 100 µg/ml) produced a CCK output of 2.3 ± 0.6, 5.1 ± 0.4, and 8.5 ± 0.9 fmol, respectively (10 and 100 µg/ml both P < 0.05 vs. basal). BBL (1, 10, and 100 µg/ml) had no significant effect on CCK output, which was 1.4 ± 0.5, 1.4 ± 0.6, and 2.0 ± 0.7 fmol, respectively.
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Response to perifused mucosal cells after repeated exposure to lectins. After repeated exposure to the lectins (100 µg), the cells responded with similar values as reported on initial exposure; values for basal, KCl, SBL, PNL, WGL, and BBL were 1.3 ± 0.5, 7.5 ± 0.5, 7.1 ± 0.4, 4.8 ± 0.3, 5.0 ± 0.5, and 1.1 ± 0.6 fmol, respectively. Perifusion of the cells with HEPES containing the corresponding sugars of the lectins restored basal output to normal.
Stability of SBL, PNL, WGL, and BBL in Activated Pancreatic Juice
Incubation of SBL and PNL (84 µg) in activated pancreatic juice diminished their hemagglutinating activity by 5% at 30 min and 15% at 60 min. Incubation of WGL (84 µg) diminished its hemagglutinating activity by 20% at 30 min and 35% at 60 min, whereas the hemagglutinating activity of BBL (84 µg) was diminished by 30% at 30 min and 35% at 60 min.Effect of Lectins on Trypsin Activity
Incubation of 100 µg trypsin with SBL, PNL, WGL, or BBL (84 µg) had no significant effect on its enzyme activity. Trypsin activity in the presence of the lectins was 97%, 100%, 98%, and 100% of control, respectively. ![]() |
DISCUSSION |
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We have already shown that SBL is a potent releaser of CCK and thus stimulates pancreatic output in anesthetized rats (14). The present work confirms this and shows that some, but not all, lectins have the same effect. CCK release and pancreatic protein output were stimulated by SBL and PNL, which bind motifs including D-galactose and N-acetyl-D-galactosamine, and by WGL, which binds to a motif including N-acetyl-D-glucosamine. BBL, which binds to mannose and glucose, did not release CCK and had no effect on pancreatic protein output. Studies using an isolated perifused cell preparation showed that the CCK response to SBL, PNL, and WGL was clearly dose dependent. In addition, their effects were dependent on the presence of extracelluar calcium. The response to the lectins was blocked in the presence of their competing sugars, which indicates that the lectins had to bind to their specific carbohydrate motifs to have an effect.
The CCK-releasing effect of raw soy flour was initially attributed to the trypsin inhibitors that it contains (9, 21). The laboratory of Pusztai (9) produced the first evidence that SBL might be involved. Dietary supplementation with this lectin led to growth and an increase in the polyamine content of the pancreas in rats (9). Pusztai et al. (27) also recently showed that the red kidney bean lectin phytohemagglutinin, which binds to complex motifs including N-acetyl-D-galactosamine, also releases CCK.
How lectins release CCK is not clearly understood. Cell damage does not appear to be involved, because CCK release in vitro was not diminished on repeat exposure to lectin. The present study shows that lectin-stimulated CCK-release is dependent on the presence of extracellular calcium.
Liddle et al. (3, 23) have shown that an influx of calcium is involved when a variety of stimuli release CCK from native CCK cells and the CCK-releasing cell line STC-1. Lectins might release CCK by activating mechanisms involved in CCK release such as potassium (35) or calcium channels or receptors for any of the various factors that release CCK (12, 20, 35, 36). CCK-releasing peptides are trypsin sensitive, but the lectins had no effects on the activity of this enzyme. The known effects of lectins on intestinal cells provide further clues. These include elevations in intracellular calcium. A rise in intracellular calcium stimulated by WGL in intestinal 407 cells was largely due to an influx of extracellular calcium (32).
After ingestion, lectins bind to the luminal surface of intestinal cells, especially in the upper small intestine (17), where CCK cells are located (20). Ultrastructural changes occur, particularly affecting the microvilli (11, 17, 22, 34). Responses include increases in the synthesis and uptake of polyamines and elevations of markers of proliferation, such as thymidine uptake, DNA content, and mitotic activity (1). Similar changes in CCK cells might lead to release of CCK peptides.
Responses of intestinal cells are related to the affinity of lectins for the cell membrane (19). Also, the stimulatory effect of lectins on intestinal cells is generally greatest if they bind motifs that include N-acetyl-D-galactosamine and least if they bind to mannose or glucose (8). The present results suggest a similar relationship between lectin specificity and CCK-releasing effect.
The relative CCK-releasing effects of the lectins were also related to their resistance to degradation by bile-pancreatic juice. SBL and PNL, which bind N-acetyl-D-galactosamine, survived best, and BBL, which binds to mannose, was lost most rapidly in activated bile-pancreatic juice. This does not appear to be a general rule however. Pusztai et al. (26) also found that SBL survived better than BBL in the intestine of rats but that snowdrop (Galanthus nivalis) lectin, which binds to mannose, survived even better than SBL. Differences in the degradation of lectins in the intestinal lumen probably did not contribute to the differences in their CCK-releasing effects in the present study, because they were administered with SBTI. Furthermore, their respective potencies were similar in vitro in the absence of digestive enzymes.
Studies in laboratory animals show that ingested lectins have a wide range of effects that might be relevant to human diseases. These included changes in the differentiation (13) as well as the proliferation of intestinal (see above) and colonic cells (29, 30). The growth of implanted tumor cells can also be affected by ingested lectins (25). Dietary lectins may affect the intestinal flora (28), and bacterial lectins can activate intestinal cells (10).
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ACKNOWLEDGEMENTS |
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We thank Dr. R. A. Liddle for providing technical advice regarding the perifused cell preparation.
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FOOTNOTES |
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M. Jordinson was supported by a Project Grant from the Wellcome Trust and R. Playford was supported by the Medical Research Council.
Address for reprint requests: J. Calam, Gastroenterology Laboratory, Dept. of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 ONN, UK.
Received 13 November 1996; accepted in final form 9 July 1997.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Banwell, J. G.,
R. Howard,
I. Kabir,
T. E. Adrian,
R. H. Diamond,
and
C. Abramowsky.
Small intestinal growth caused by feeding red kidney bean phytohemagglutinin lectin to rats.
Gastroenterology
104:
1669-1677,
1993[Medline].
2.
Borgstrom, A.,
C. E. Albertsson,
and
B. Borgstrom.
Human pancreatic proenzymes are activated at different rates in vitro.
Scand. J. Gastroenterol.
28:
455-459,
1993[Medline].
3.
Bouras, E. P.,
M. A. Misukonis,
and
R. A. Liddle.
Role of calcium in monitor peptide-stimulated cholecystokinin release from perifused intestinal cells.
Am. J. Physiol.
262 (Gastrointest. Liver Physiol. 25):
G791-G796,
1992
4.
Brady, P. G.,
A. M. Vannier,
and
J. G. Banwell.
Identification of the dietary lectin, wheat germ agglutinin, in human intestinal contents.
Gastroenterology
75:
236-239,
1978[Medline].
5.
Calam, J.,
J. C. Bojarski,
and
C. J. Springer.
Raw soya-bean flour increases cholecystokinin release in man.
Br. J. Nutr.
58:
175-179,
1987[Medline].
6.
Crass, R. A.,
and
R. G. Morgan.
The effect of long-term feeding of soya-bean flour diets on pancreatic growth in the rat.
Br. J. Nutr.
47:
119-129,
1982[Medline].
7.
Erlanger, B. F.,
N. Kokowski,
and
W. Cohen.
The preparation and properties of two new chromogenic substrates of trypsin.
Arch. Biochem. Biophys.
95:
271-278,
1961.
8.
Goldstein, I. J.,
and
R. D. Poretz.
Isolation, physicochemical characterisation, and carbohydrate-binding specificity of lectins.
In: The Lectins: Properties, Functions, and Applications in Biology and Medicine, edited by I. E. Liener,
N. Saron,
and I. J. Goldstein. London: Academic, 1986, p. 33-237.
9.
Grant, G.,
S. Bardocz,
D. S. Brown,
W. B. Watt,
J. C. Stewart,
and
A. Pusztai.
Involvement of polyamines in pancreatic growth induced by dietary soyabean, lectin or trypsin inhibitors.
Biochem. Soc. Trans.
18:
1009-1010,
1990[Medline].
10.
Grant, G.,
S. Bardocz,
S. W. Ewen,
D. S. Brown,
T. J. Duguid,
A. Pusztai,
D. Avichezer,
D. Sudakevitz,
A. Belz,
N. C. Garber,
and
N. Gilboa-Garber.
Purified Pseudomonas aeruginosa PA-I lectin induces gut growth when orally ingested by rats.
FEMS Immunol. Med. Microbiol.
11:
191-195,
1995[Medline].
11.
Hart, C. A.,
R. M. Batt,
J. R. Saunders,
and
B. Getty.
Lectin-induced damage to the enterocyte brush border. An electron-microscopic study in rabbits.
Scand. J. Gastroenterol.
23:
1153-1159,
1988[Medline].
12.
Herzig, K. H.,
I. Schon,
K. Tatemoto,
Y. Ohe,
Y. Li,
U. R. Folsch,
and
C. Owyang.
Diazepam binding inhibitor is a potent cholecystokinin releasing peptide in the intestine.
Proc. Natl. Acad. Sci. USA
93:
7927-7932,
1996
13.
Jordinson, M., J. Calam, and M. Pignatelli. Broad bean
lectin increases morphological differentiation and inhibits
proliferation of colon carcinoma cells (Abstract).
Gut 39, Suppl. 3: A212, 1996.
14.
Jordinson, M.,
P. H. Deprez,
R. J. Playford,
S. Heal,
T. C. Freeman,
M. Alison,
and
J. Calam.
Soybean lectin stimulates pancreatic exocrine secretion via CCK-A receptors in rats.
Am. J. Physiol.
270 (Gastrointest. Liver Physiol. 33):
G653-G659,
1996
15.
Judd, W. J.
Methods in Immunohematology. Durham, NC: Montgomery Scientific Publications, 1994.
16.
Kilpatrick, D. C.,
A. Pusztai,
G. Grant,
C. Graham,
and
S. W. Ewen.
Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects.
FEBS Lett.
185:
299-305,
1985[Medline].
17.
King, T. P.,
A. Pusztai,
and
E. M. Clarke.
Immunocytochemical localization of ingested kidney bean (Phaseolus vulgaris) lectins in rat gut.
Histochem. J.
12:
201-208,
1980[Medline].
18.
Koninkx, J. F.,
D. S. Brown,
W. Kok,
H. G. Hendriks,
A. Pusztai,
and
S. Bardocz.
Polyamine metabolism of enterocyte-like Caco-2 cells after exposure to Phaseolus vulgaris lectin.
Gut
38:
47-52,
1996[Abstract].
19.
Koninkx, J. F.,
H. G. Hendriks,
J. M. van Rossum,
T. S. van den Ingh,
and
J. M. Mouwen.
Interaction of legume lectins with the cellular metabolism of differentiated Caco-2 cells.
Gastroenterology
102:
1516-1523,
1992[Medline].
20.
Liddle, R. A.
Cholecystokinin.
In: Gut Peptides, edited by J. H. Walsh,
and G. J. Dockray. New York: Raven, 1994, p. 175-216.
21.
Liener, I. E.
Possible adverse effects of soybean anticarcinogens.
J. Nutr.
125:
744S-750S,
1995[Medline].
22.
Lorenzsonn, V.,
and
W. A. Olsen.
In vivo responses of rat intestinal epithelium to intraluminal dietary lectins.
Gastroenterology
82:
838-848,
1982[Medline].
23.
Mangel, A. W.,
L. Scott,
and
R. A. Liddle.
Depolarizationstimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells.
Am. J. Physiol.
270 (Gastrointest. Liver Physiol. 33):
G287-G290,
1996
24.
Nachbar, M. S.,
and
J. D. Oppenheim.
Lectins in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature.
Am. J. Clin. Nutr.
33:
2338-2345,
1980[Abstract].
25.
Pryme, I. F.,
A. J. Pusztai,
and
S. Bardocz.
A diet containing the lectin phytohaemagglutinin (PHA) slows down the proliferation of Krebs II cell tumours in mice.
Cancer Lett.
76:
133-137,
1994[Medline].
26.
Pusztai, A., S. W. Ewen, G. Grant, W. J. Peumans, E. J. van Damme, L. Rubio, and S. Bardocz.
Relationship between survival and binding of plant lectins during
small intestinal passage and their effectiveness as growth factors.
Digestion 46, Suppl. 2: 308-316, 1990.
27.
Pusztai, A.,
G. Grant,
K. Baintner,
S. Bardocz,
K. H. Herzig,
U. R. Folsch,
and
R. Nustede.
Orally administered lectins induce release of CCK from the duodenum and the growth of the pancreas which is blocked by CCK-A receptor antagonists (Abstract).
Regulatory Peptides
64:
156,
1996.
28.
Pusztai, A.,
G. Grant,
R. J. Spencer,
T. J. Duguid,
D. S. Brown,
S. W. Ewen,
W. J. Peumans,
E. J. van Damme,
and
S. Bardocz.
Kidney bean lectin-induced Escherichia coli overgrowth in the small intestine is blocked by GNA, a mannose-specific lectin.
J. Appl. Bacteriol.
75:
360-368,
1993[Medline].
29.
Ryder, S. D.,
N. Parker,
D. Ecclestone,
M. T. Haqqani,
and
J. Rhodes.
Peanut lectin stimulates proliferation of colonic explants from patients with inflammatory bowel disease and colon polyps.
Gastroenterology
106:
117-124,
1994[Medline].
30.
Ryder, S. D.,
J. A. Smith,
E. G. H. Rhodes,
N. Parker,
and
J. M. Rhodes.
Proliferative responses of HT29 and CaCo2 human colorectal cancer cells to a panel of lectins.
Gastroenterology
106:
85-93,
1994[Medline].
31.
Ryder, S. D.,
J. A. Smith,
and
J. M. Rhodes.
Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells.
J. Natl. Cancer Inst.
84:
1410-1416,
1992[Abstract].
32.
Sjolander, A.
Direct effects of wheat germ agglutinin on inositol phosphate formation, and cytosolic-free calcium level in intestine 407 cells.
J. Cell. Physiol.
134:
473-478,
1988[Medline].
33.
Sjolander, A.,
and
K. E. Magnusson.
Effects of wheat germ agglutinin on the cellular content of filamentous actin in intestine 407 cells.
Eur. J. Cell Biol.
47:
32-35,
1988[Medline].
34.
Sjolander, A.,
K. E. Magnusson,
and
S. Latkovic.
Morphological changes of rat small intestine after short-time exposure to concanavalin A or wheat germ agglutinin.
Cell Struct. Funct.
11:
285-293,
1986[Medline].
35.
Spannagel, A. W.,
G. M. Green,
D. Guan,
R. A. Liddle,
K. Faull,
and
J. R. J. Reeve.
Purification and characterization of a luminal cholecystokinin-releasing factor from rat intestinal secretion.
Proc. Natl. Acad. Sci. USA
93:
4415-4420,
1996
36.
Yamanishi, R.,
J. Kotera,
T. Fushiki,
T. Soneda,
T. Saitoh,
T. Oomori,
T. Satoh,
and
E. Sugimoto.
A specific binding of the cholecystokinin-releasing peptide (monitor peptide) to isolated rat small-intestinal cells.
Biochem. J.
291:
57-63,
1993[Medline].