Department of Physiology, University of British Columbia, Vancouver, Canada V6T 1Z3
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The profile of hormone secretion from the gastrointestinal tract on food ingestion depends to a great extent on the composition of the meal. High levels of protein result in a quantitatively and qualitatively different response compared with a meal rich in fats. The outstanding question is whether this differential response is driven by the ability of gastroenteric endocrine cells to directly sense the contents of the lumen via apical microvilli. Alternative effectors would include activation of the intrinsic and extrinsic innervation or other epithelial cell populations. The data available indicate that the role of the gastrointestinal innervation is relatively limited and is probably a major factor only in the postprandial responses of hormones released from endocrine cells in the distal small intestine. However, whether nutrients directly stimulate gastroenteric endocrine cells or another epithelial cell type has yet to be established.
enteric endocrine cells; microvilli; gastrin; cholesystokinin; glucagon-like peptide-1
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
THE PHYSIOLOGICAL RESPONSE of the gastrointestinal tract to incoming nutrients has to be coordinated to allow correct processing of an ingested meal. For example, a meal high in protein requires the secretion of proteolytic enzymes from the pancreas to break down complex proteins into single amino acids and dipeptides that can be transported into the enterocytes lining the upper intestine. Equally, ingestion of fats requires the secretion of bile to promote the formation of chylomicrons for absorption of triglyceride and long-chain fatty acids. In both cases, insulin secretion from the endocrine pancreas is stimulated to facilitate uptake of the absorbed glucose, amino acids, and fat.
This coordination is achieved by the release of hormones from endocrine cells lining the stomach and intestine. The critical hormones involved in this process are gastrin, CCK, secretin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). The ability of luminal nutrients to stimulate the release of gastroenteric hormones has been extensively studied by monitoring plasma levels after nutrient ingestion. By use of defined meals and individual nutrients (including alcohol and caffeine), the precise components of a meal capable of stimulating hormone release can be determined. The advantage of such studies is the noninvasive nature of the preparation, allowing collection of data from humans as well as animal models. The in vivo data have provided important information on the sensitivity of endocrine cell populations to individual nutrients and a comparison of the differential sensitivity of endocrine cells to nutrients across species. Unfortunately, such experiments cannot determine whether the effect of the ingested nutrient occurs directly on the endocrine cell or through an intermediary, such as activation of the intrinsic and extrinsic innervation or other cell types within the mucosal epithelium.
The development of isolated endocrine cell cultures removed some of the factors complicating the interpretation of in vivo data. Although these culture preparations are not 100% pure endocrine cells, the neuronal cells, the circulating factors, and the majority of the cells in the lamina propria have been eliminated. The remaining cells are epithelial in origin and therefore could serve as nutrient sensors in the gastrointestinal tract. Thus, if a nutrient added to these cultures stimulates hormone secretion, the isolated cell preparation can be used discriminately between an effect on epithelial cells as opposed to an effect on intrinsic and extrinsic nerve fibers, mast cells, and other nonepithelial cells. However, whether the nutrient acted directly on the endocrine cells within the preparation remains to be seen. We will look briefly at what is known about the ability of different nutrients to stimulate endocrine secretion.
![]() |
GASTRIC CELLS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Of the endocrine cells in the stomach, the gastrin-containing G cell can be used as an example of luminal nutrient sensitivity. Gastrin release is increased by luminal calcium, amino acids, and fermented glucose but not by glucose itself or carbohydrates and fat (3, 24, 28). A comparison of the ability of food instilled into the stomach compared with the upper intestine showed that intragastric delivery produced the greatest increase in plasma gastrin (18). Although part of the intragastric response is probably due to stimulation of vagal efferents by gastric distension, local stimulation of the G cells is also an important component. The ability of individual dietary factors to stimulate G cell secretion has been examined in a number of experiments using isolated antral cell cultures.
Calcium added to antral cell cultures stimulates gastrin release at concentrations well within physiological limits, suggesting a direct effect on the G cells. We have recently shown that the G cells express the calcium-sensing receptor (CaR) on both the apical and basolateral membrane in the antrum and in primary cultures (22), indicating that calcium can trigger gastrin release by interacting with a cell surface "sensory" protein. The presence of the CaR on the apical membrane and the rapid rise in intracellular calcium in G cells exposed to increased extracellular calcium strongly suggest that the apical CaR is capable of monitoring luminal calcium levels (22).
Of the amino acids present within a normal diet, phenylalanine and tryptophan are the most effective in stimulating gastrin release. To date, no cell surface receptors for either amino acid have been identified, whereas there is evidence to suggest that intracellular decarboxylation to the amine is required to stimulate hormone release. In rats, the ability of amino acids to release gastrin was prevented by addition of the decarboxylase inhibitor deoxypyridoxine (19). However, in isolated canine antral cells enzyme inhibition did not prevent the stimulatory effect of phenylalanine (5). The data in the latter study suggest that both amines and amino acids are capable of stimulating gastrin release, acting through different pathways (5). In either case, it appears that transport of the amino acid into the endocrine cell is required; therefore, the relevant transport proteins should be present on the microvilli of the G cells.
![]() |
UPPER SMALL INTESTINE |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The majority of food absorption occurs in the distal duodenum and jejunum. It is no surprise, therefore, that the endocrine cells located in this region are highly sensitive to luminal nutrient concentrations. Of the ingested food groups, fat is the most effective in stimulating upper intestinal endocrine cells, increasing the secretion of CCK, GIP, and secretin. The effect of fat depends on hydrolysis and formation of chylomicrons and can be prevented by substitution of digestible fat with sucrose polyester (20) or by the addition of surfactants to prevent chylomicron formation (for a full discussion of the effect of fat, see Ref. 23). The dependence on chylomicron formation indicates that hormone stimulation requires either entry of hydrolyzed fat into the epithelial cells or an interaction between the chylomicrons and the microvillus membrane. In addition to the effect of fat itself, bile salts released into the lumen in response to incoming fat modulate hormone release. Conjugated bile acids such as chenodeoxycholate stimulate, whereas unconjugated bile acids inhibit CCK release (21).
Glucose infusion into the duodenum/jejunum stimulates the release of GIP and CCK but not secretin (1, 15). The hypertonicity of the glucose solution does not itself stimulate hormone release because other hypertonic solutions are ineffective (3). The ability of glucose to stimulate hormone release can be prevented by inhibition of the sodium-dependent glucose transporter by phloridzin, suggesting that entry into the endocrine cell is required. Whether the enteric endocrine cells express the ATP-gated potassium channel known to be involved in glucose-stimulated insulin release has yet to be established. Interestingly, the hormones released by glucose can in turn influence hexose absorption. In an isolated jejunal preparation, infusion of CCK into the mesenteric artery reduced absorption of labeled hexoses infused into the lumen (11). These data suggest a direct interplay between glucose-stimulated hormone release and glucose uptake by enterocytes.
Secretin is unaffected by instillation of protein into the small intestine; however, GIP and CCK are released in response to selected amino acids. Specifically, histidine and arginine stimulate GIP, whereas tryptophan and phenylalanine stimulate CCK both in vivo and in vitro (17, 24). In vivo, if protein digestion is prevented by inhibition of pancreatic proteases, the ability of amino acids but not proteins to stimulate hormone secretion is maintained (29). These data indicate that enteric endocrine cells possess amino acid transporters in the brush-border membranes that mediate amino acid uptake into the cell before hormone stimulation.
![]() |
DISTAL SMALL INTESTINE |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The vast majority of food entering the small intestine is cleared by the duodenum and jejunum. Only if there is a problem with normal absorptive processes (such as celiac disease and dumping syndrome) will significant amounts of luminal nutrients reach the ileal mucosa. Of the endocrine cells in the distal gut, the GLP-1 secreting L cell and the neurotensin-secreting N cell are the most abundant. Fat and carbohydrate in the lumen release both hormones in whole animal models; however, only fat is effective in cultured cell preparations (4, 6, 8). It is unlikely under normal circumstances that either nutrient plays a significant role in the stimulation of ileal endocrine cells because both are absorbed in the upper intestine. It is more probable that neuroendocrine pathways initiated in the upper intestine are the relevant stimuli. Although not nutrients, bile salts released by the entry of fat into the upper small intestine are absorbed by the distal small intestine and are present in high concentrations in the lumen. In rats, a luminal perfusion of taurocholate at physiological concentrations results in the release of GLP-1, suggesting an interaction between L cells and bile salts (6).
The importance of the ability of ileal endocrine cells to sense luminal fats is that neurotensin and GLP-1 act as an "ileal brake," slowing gastric emptying and thus decreasing the volume of incoming chyme. The ability of fat to stimulate ileal hormone release is similar to that of the upper intestinal cells, with long-chain fatty acids being the most effective.
![]() |
MECHANISMS FOR NUTRIENT STIMULATION OF ENDOCRINE CELLS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
There are at least three ways in which the endocrine cells can
selectively respond to luminal nutrients:
1) the cells can directly monitor
the contents of the gut lumen via the receptors/transporters present in
the apical microvilli; 2) nutrients
can stimulate the intrinsic gastroenteric nervous system and/or
extrinsic nervous system that subsequently stimulates the endocrine
cells; or 3) a cell within the
epithelial lining may act as an intermediary by sensing the contents of
the gut lumen and releasing a nonhormonal factor to act in a paracrine
manner to stimulate adjacent endocrine cells (Fig.
1). Each of these mechanisms will be
examined in turn.
|
Direct monitoring of luminal nutrients by endocrine cells. The morphology of the endocrine cells would facilitate this function because the cells are polarized, with long microvilli at the apical surface projecting into the lumen of the stomach or intestine. These microvilli may function to "sense" the composition of the gastric juice or intestinal chyme.
Microvilli are composed of a central core of actin filaments connected to the cortical web underlying the plasma membrane and are enriched for the ezrin radixin moesin (ERM) protein ezrin that serves to anchor membrane proteins within microvilli (2). The presence of tight junctions at the lateral margins of the apical side of the intestinal epithelial cells restricts microvilli to the surface of the cells adjacent to the lumen and regulates paracellular transport. Interestingly, endocrine cells display microvilli that are longer than those of the surrounding enterocytes projecting out into the gut lumen, and we have recently found that these are strongly immunostained by antibodies to ezrin (Buchan, unpublished data). Specific proteins are targeted for delivery to the apical domain of polarized cells, such as transporters, receptors, and proteolytic enzymes; the location of these proteins is critical to the sensory function of the microvilli. Although the precise nature of the proteins concentrated in the microvilli of endocrine cells has yet to be established, it is probable that many will be the same as those identified on the surrounding enterocytes. In enterocytes, peptidases, disaccharidases, bile salt, and calcium receptors, as well as transporters for glucose and amino acids, have been localized in brush-border vesicles. The apical peptidases and amino acid transporters would be ideally placed to monitor the concentration of protein in the luminal chyme as well as to facilitate absorption. The luminal carbohydrate loading would be monitored by glucose transport because the uptake of other hexoses has no effect on hormone release. The presence of bile acid receptors on the brush-border membrane suggests that these may serve as sensors transducing the stimulation of CCK, GLP-1, and neurotensin cells by luminal bile (6, 21). Whether hormone release can be initiated by chylomicrons interacting with these receptors is presently unknown. A common structure in all gastrointestinal microvilli is the presence of an overlying glycocalyx, and the external domain of many of the surface receptors and enzymes projects into this region. A structural feature of the external domains of these proteins is the presence of sugar residues, such as mannose and galactose, attached as long side chains to the peptide backbone. Each protein is glycosylated to a different extent with a specific composition and sequence of sugars. This property of surface proteins can be used to differentiate different gastrointestinal cell lineages through the use of lectins. Lectins are a group of proteins with clearly defined carbohydrate-binding specificities usually isolated from plant sources and present in most diets. Although some murine intestinal cell lineages show specific lectin markers, enteroendocrine cells were detected by lectins that also bound to a number of other epithelial cell types (7). These data would favor the common expression of glycoproteins on the microvilli of gastroenteric endocrine cells and adjacent epithelial cells. Interestingly, three of the lectins that detected enteroendocrine cells in murine intestine were specific for fucosyl residues (7). In several species, including humans, the binding of fucose-specific lectins was found to be concentrated in the glycocalyx overlying the microvilli of enteroendocrine cells but not adjacent enterocytes (9). This localization led to the suggestion that fucose-containing glycoproteins could play a role in the sensory function of the microvilli. The second group of lectins that detected murine enteroendocrine cells was galactosyl specific. Of these, peanut agglutinin has also been shown to stimulate the release of gastrin and CCK when infused into the intestine of rats (14). These data suggest that if the glycoproteins bound by peanut agglutinin on the apical microvilli were identified one or more could also serve a sensory function in the endocrine cells and would support a direct sensory function for the brush-border membrane. A cautionary note, however, is that two lectins identified as hormone stimulating in rats, phytohemagglutinin and wheat germ agglutinin, were not observed to bind to murine enteroendocrine cells, suggesting either an indirect route of action or species specificity in the surface glycoproteins bound by the lectins.Intrinsic and extrinsic innervation. Elegant experiments completed in whole animals have examined the role of the intestinal innervation in mediating the hormonal response to nutrients. The hormone GLP-1, produced by cells in the distal intestine, is a glucose-dependent stimulant of insulin secretion that is not itself stimulated by luminal glucose (4, 25). It has been suggested that GLP-1 secretion after a meal is stimulated by GIP released from the upper intestine in response to ingestion of glucose or fat. To examine this further, rats were given an intraduodenal infusion of fat with and without gut transection (which removes descending stimulatory pathways in the enteric nervous system) and subdiaphragmatic vagotomy. Although transection delayed the rise in GLP-1, vagotomy abolished the GLP-1 response to fat but not GIP (24). In dogs, neither cooling of the cervical vagus nor atropine administration blocked the release of GIP in response to intraduodenal glucose or a defined meal (10). These data would be consistent with the ability of upper intestinal endocrine cells to directly sense luminal nutrients (GIP response), whereas the postprandial rise in hormones from the distal intestine requires input from the intrinsic and extrinsic innervation (GLP-1 response).
Intermediary epithelial cells.
A second cell type identified in the gastroenteric
epithelium with long microvilli projecting above the surrounding
enterocytes but lacking intracellular secretory vesicles typical of
enteroendocrine cells is the "brush cells." Brush cells have
recently been shown to express the chemosensory heterotrimeric G
protein, -gustducin, originally isolated from the taste receptor
cells in the tongue. Interestingly, these cells also stain positively
for nitric oxide synthase, suggesting that nitric oxide released from
brush cells monitoring luminal nutrients could act on adjacent
endocrine cells to stimulate hormone secretion (12). Clearly, further
experiments need to be completed to determine whether inhibitors of
nitric oxide synthase such as
NG-nitro-L-arginine
methyl ester have an effect on nutrient-stimulated hormone release
either in vivo or from cultured cell preparations.
![]() |
SUMMARY AND FUTURE DIRECTIONS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The major difficulty in establishing the precise sensory functions of gastroenteric endocrine cells is the lack of a pure, polarized endocrine cell preparation. All primary cell cultures available are a mixed population with a substantial proportion of nonendocrine epithelial cells. If these are further purified to give predominantly endocrine cells (80-90% pure), the cell yield is low and the cultured cells remain as single spherical cells and do not re-polarize (27). This makes the study of the sensory function of the apical pole of the cells impossible to determine. Although the intestinal endocrine cell line STC-1 has been used to examine hormone secretion in response to a variety of nutrients, these cells do not have a polarized organization in culture. In addition, the cells express multiple hormones and cannot be taken as a model of normal enteric endocrine cells (16, 26).
A variety of assumptions have been made concerning the sensory ability of gastroenteric endocrine cells on the basis of hormone release in response to the addition of selected nutrients to cultured cells. In these preparations, a rapid rise in intracellular calcium is observed on addition of dietary factors (e.g., calcium and glucose). The kinetics of this response suggest a direct action of the nutrient on the endocrine cells, with an insufficient time delay before onset for the release of an intermediary from a cocultured cell. However, it is difficult to assess whether stimulation occurred through the apical or basolateral surface of the endocrine cell. Although the gastroenteric endocrine cells repolarize in culture, there is limited cell division; therefore, confluent monolayers are not obtained, making it difficult to distinguish vectorial responses. In fact, to my knowledge, there is no unequivocal evidence for direct stimulation of gastroenteric endocrine cells by nutrients.
In the absence of a workable culture preparation to establish the apical responses of enteric endocrine cells, the onus appears to be on studies designed to establish the presence of specific apical proteins in the endocrine cell microvilli. These studies should involve both cultured endocrine cells and cells in situ in the gastrointestinal tract. If unique proteins can be identified, then whole animal and cell culture studies using gene knockout technology can be initiated to determine if these proteins play a role in the hormone-specific responses to nutrients. There is sufficient information already available to indicate that intrinsic and extrinsic innervation are not required for nutrient-stimulated hormone release; the major question remaining is whether other epithelial cells, such as the brush cells, play a critical role in nutrient sensing.
![]() |
ACKNOWLEDGEMENTS |
---|
A. M. J. Buchan is funded by the Medical Research Council of Canada.
![]() |
FOOTNOTES |
---|
* Third in a series of invited articles on Nutrient Tasting and Signaling Mechanisms in the Gut.
Address for reprint requests and other correspondence: A. M. J. Buchan, Dept. of Physiology, Univ. of British Columbia, 2146 Health Sciences Mall, Vancouver, Canada V6T 1Z3 (E-mail: buchan{at}cs.ubc.ca).
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Boden, G.,
N. Essa,
O. E. Owen,
and
F. A. Reichle.
Effects of intraduodenal administration of HCl and glucose on circulating immunoreactive secretin and insulin concentrations.
J. Clin. Invest.
53:
1185-1193,
1974[Medline].
2.
Bretscher, A.,
D. Reczek,
and
M. Berryman.
Ezrin: a protein requiring conformation activation to link microfilaments to the plasma membrane in the assembly of cell surface structures.
J. Cell Sci.
110:
3011-3018,
1997
3.
Chari, S. T.,
H. Harder,
S. Teyseen,
C. Knodel,
R. L. Riepl,
and
M. V. Singer.
Effect of beer, yeast fermented glucose and ethanol on pancreatic enzyme secretion in healthy human subjects.
Dig. Dis. Sci.
41:
1216-1224,
1996[Medline].
4.
Damholt, A. B.,
A. M. J. Buchan,
and
H. Kofod.
Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose-dependent-insulinotropic peptide but unaffected by glucose.
Endocrinology
139:
2085-2091,
1998
5.
Delvalle, J.,
and
T. Yamada.
Amino acids and amines stimulate gastrin release from canine antral G cells via different pathways.
J. Clin. Invest.
85:
139-143,
1990[Medline].
6.
Dumoulin, V.,
F. Moro,
A. Barcelo,
T. Dakka,
and
J. C. Cuber.
Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum.
Endocrinology
139:
3780-3786,
1998
7.
Falk, P.,
K. A. Roth,
and
J. I. Gordon.
Lectins are sensitive tools for defining the differentiation programs of mouse gut epithelial cell lineages.
Am. J. Physiol.
266 (Gastrointest. Liver Physiol. 29):
G987-G1003,
1994
8.
Ferris, C. F.,
M. J. Armstrong,
J. K. George,
C. A. Stevens,
R. E. Carraway,
and
S. E. Leeman.
Alcohol and fatty acid stimulation of neurotensin release from rat small intestine.
Endocrinology
116:
1133-1138,
1985[Abstract].
9.
Gebert, A.,
and
Y. Cetin.
Expression of fucose residues in entero-endocrine cells.
Histochem. Cell Biol.
109:
161-165,
1998[Medline].
10.
Greenberg, G. R.,
and
S. Pokol-Daniel.
Neural modulation of glucose-dependent insulinotropic peptide (GIP) and insulin secretion in conscious dogs.
Pancreas
9:
531-535,
1994[Medline].
11.
Hirsh, A. J.,
R. Tsang,
S. Kammila,
and
C. I. Cheeseman.
Effect of cholecystokinin and related peptides on jejunal transepithelial hexose transport in the Sprague-Dawley rat.
Am. J. Physiol.
271 (Gastrointest. Liver Physiol. 34):
G755-G761,
1996
12.
Hofer, D.,
T. Jons,
J. Kraemer,
and
D. Drenckhahn.
From cytoskeleton to polarity and chemoreception in the gut epithelium.
Ann. NY Acad. Sci.
859:
75-84,
1998
14.
Jordinson, M.,
R. J. Playford,
and
J. Calam.
Effects of panel of dietary lectins on cholecystokinin release in rats.
Am. J. Physiol.
273 (Gastrointest. Liver Physiol. 36):
G946-G950,
1997
15.
Kieffer, T. J.,
A. M. J. Buchan,
H. Barker,
J. C. Brown,
and
R. A. Pederson.
Release of gastric inhibitory polypeptide (GIP) from cultured canine endocrine cells.
Am. J. Physiol.
267 (Endocrinol. Metab. 30):
E489-E496,
1994
16.
Kieffer, T. J.,
Z. Huang,
C. H. McIntosh,
A. M. J. Buchan,
J. C. Brown,
and
R. A. Pederson.
Gastric inhibitory polypeptide release from a tumor-derived cell line.
Am. J. Physiol.
269 (Endocrinol. Metab. 32):
E316-E322,
1995
17.
Koop, I.,
and
A. M. J. Buchan.
CCK release from isolated canine epithelial cells in short term culture.
Gastroenterology
102:
28-34,
1992[Medline].
18.
Ledeboer, M.,
A. A. Masclee,
I. Biemond,
and
C. B. Lamers.
Effect of intragastric or intraduodenal administration of a polymeric diet on gall bladder motility, small-bowel transit time, and hormone release.
Am. J. Gastroenterol.
93:
2089-2096,
1998[Medline].
19.
Lichtenberger, L. M.,
R. Lelansorne,
and
L. A. Graziani.
Importance of amino acid uptake and decarboxylation in gastrin release from isolated G cells.
Nature
295:
698-700,
1982[Medline].
20.
Maas, M. I.,
W. P. Hopman,
T. Van Der Wijk,
M. B. Katan,
and
J. B. Jansen.
Sucrose polyester does not inhibit gastric acid secretion or stimulate cholecystokinin release in men.
Am. J. Clin. Nutr.
65:
761-765,
1997[Abstract].
21.
Miyasaka, K.,
A. Funakoshi,
F. Shikado,
and
K. Kitani.
Stimulatory and inhibitory effects of bile salts on rat pancreatic secretion.
Gastroenterology
102:
598-604,
1992[Medline].
22.
Ray, J. M.,
P. E. Squires,
S. B. Curtis,
R. M. Meloche,
and
A. M. J. Buchan.
Expression of the calcium-sensing receptor on human antral gastrin cells in culture.
J. Clin. Invest.
99:
2328-2333,
1997
23.
Raybould, H. E.
Sensing of lipid by the intestinal mucosa.
Am. J. Physiol.
277 (Gastrointest. Liver Physiol. 40):
G751-G755,
1999
24.
Rerat, A.,
J. A. Chayvialle,
J. Kande,
P. Vaissade,
P. Vaugelade,
and
T. Bourrier.
Metabolic and hormonal effects of test meals with various protein contents in pigs.
Can. J. Physiol. Pharmacol.
63:
1547-1559,
1985[Medline].
25.
Rocca, A. S.,
and
P. L. Brubaker.
Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion.
Endocrinology
140:
1687-1694,
1999
26.
Scott, L.,
V. Prpic,
W. D. Capel,
S. Basavappa,
A. W. Mangel,
T. W. Gettys,
and
R. A. Liddle.
-Adrenergic regulation of cholecystokinin secretion in STC-1 cells.
Am. J. Physiol.
270 (Gastrointest. Liver Physiol. 33):
G291-G297,
1996
27.
Seensalu, R.,
D. Avedian,
R. Barbuti,
M. Song,
L. Slice,
and
J. H. Walsh.
Bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by protein kinase C, and is enhanced by disruption of rho/cytoskeletal pathways.
J. Clin. Invest.
100:
1037-1046,
1997
28.
Taylor, I. L.,
W. J. Byrne,
D. L. Christie,
M. E. Ament,
and
J. H. Walsh.
Effect of individual L-amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans.
Gastroenterology
83:
273-278,
1982[Medline].
29.
Thimister, P. W. L.,
W. P. M. Hopman,
C. E. J. Sloots,
G. Rosenbusch,
H. L. Willems,
F. J. M. Trijbels,
and
J. B. M. T. Jansen.
Role of intraduodenal proteases in plasma cholecystokinin and pancreaticobiliary responses to protein and amino acids.
Gastroenterology
110:
567-575,
1996[Medline].