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Chemosensory Perception in the Gut

Dirk Höfer, Esther Asan and Detlev Drenckhahn

D. Höfer, E. Asan, and D. Drenckhahn are in the Institute of Anatomy, Julius Maximilians University, Koellikerstr. 6, D-97070 Würzburg, Germany.

	Abstract

 
The ability of the gut mucosa to sense the chemical composition of chyme is important for gastrointestinal functions. The demonstration of gustducin and transducin, two -subunits of GTP-binding proteins involved in gustatory signal transduction, in gastrointestinal epithelial cells provides first clues to the molecular basis of enteric chemosensitivity. Nitric oxide may play a role as a secondary messenger.

	Introduction

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 
A variety of neural and humoral mechanisms regulate gastrointestinal functions preceding, accompanying, and following food intake and digestion. Different forms of sensory perception initiate and sustain the coordinated processes of gastrointestinal motility, circulation, absorption, exocrine and endocrine secretion, and satiation. In the cephalic phase of digestion, the mere imagination or the visual perception of food is able to mediate an increase in vagal firing and start gastrointestinal activity via an obviously neural pathway. On the uptake of food, the analysis of its chemical components is carried out by two different senses: olfaction and gustation. The chemosensory reception events and their signal transduction pathways have been the subject of extensive studies in recent years. Different odors and taste sensations are perceived by specialized epithelial cells. Olfactory neurons are presumably able to discriminate tens of thousands of volatile odors via specific receptor molecules. The sense of taste is comprised of four submodalities sensitive to sweet, sour, salty, and bitter, which are perceived by intraepithelial chemosensory organs of the tongue, named taste buds (4). Whereas ionic stimuli such as salt and acids interact directly with ion channels to depolarize taste receptor cells, sugars, amino acids, and most bitter-tasting compounds bind to the outside of yet-unidentified receptor molecules of the plasma membrane that are coupled to heterotrimeric GTP-binding proteins (G proteins), two -subunits of which are denoted as -gustducin and rod -transducin (4).

Olfaction and gustation work in combination to function as a kind of quality control of our food that classifies the incoming nutritional components into either usable or incompatible categories. The information perceived is transmitted to the central nervous system via olfactory and gustatory afferents, and, if the food is smelling good and tasty, swallowing is initiated.

Although olfaction and gustation are consciously perceived and thus the most obvious chemosensory events accompanying a meal, chemosensory perception in the gut is by no means restricted to these two senses. In contrast, the intestinal tract is well equipped to detect chemical components of the luminal contents (9). Chemosensory information perceived during the gastric and intestinal phases of digestion is important for the regulation of various aspects of gastrointestinal functions, such as the secretory activity of gastrointestinal glands, the resorptive activity, motility and blood supply of the intestinal tract, and satiation. However, the mechanisms involved in the perception of chemical signals, and in the signal transduction pathways of intestinal chemosensitivity, are still far from clear.

Two effects of chemical stimulants in the intestinal lumen have been well documented in recent years: first, the stimulation of neural afferent pathways, especially of intestinal vagal sensory afferent fibers, and, second, the increased release of gastrointestinal hormones from enteroendocrine cells in the intestinal epithelium (Fig. 1).

View larger version (68K): [in this window] [in a new window]   FIGURE 1. Hypothetical pathways involved in chemosensory signaling in gastrointestinal mucosa as discussed and reviewed in this paper. Primary sites of chemoreception are assumed to be located in different cell types of epithelial lining. Direct communication between epithelial cells and afferent nerve fibers is postulated to occur by signaling molecules such as peptide hormones released from enteroendocrine cells or by nitric oxide (NO) produced by nitric oxide synthase (NOS) of enterocytes and brush cells. Indirect transmission to afferent nerve fibers might be mediated by signals (chemical, mechanical) generated by subepithelial myofibroblasts, smooth muscle, or blood vessels.

	Neuronal and enteroendocrine responses to chemical components of the gut lumen

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

Alterations in the chemical composition of chyme such as acidification, alkalization, and changes in the content of fat, carbohydrates, and protein or in luminal osmolality have been shown to induce the release of a number of enteroendocrine peptides from the intestinal epithelium [gastrin, somatostatin, cholecystokinin (CCK), secretin, neurotensin, peptide YY, gastric inhibitory peptide, peptides derived from proglucagon, etc.; see, e.g., Refs. 6 and 14]. The release of specific hormones has been implied in the regulation of secretory processes in the stomach, intestine, and pancreas as well as in gastric emptying, gall bladder contraction, small intestinal motility, gastrointestinal blood flow, and satiety. Released hormones may exert their effects via an endocrine, a paracrine, or even a luminocrine pathway initiating the desired response in their target cells by stimulating specific receptors (see, e.g., Refs. 6 and 14). Additionally, recent evidence indicates that the effect of the released hormones may at least partly be neurally mediated. Thus the effects of CCK on gastrointestinal motility have been found to be mediated by CCK-induced neural reflex mechanisms (see Ref. 6).

Discharge of sensory afferents and peptide release could be described as the afferent loop of the intestinal chemosensory pathway. Although our understanding of the processes governing this afferent loop is growing rapidly, the question of how the chemical signal is perceived by or transmitted to chemoreceptive afferent fibers, and to enteroendocrine cells, has not been answered yet.

	Afferent nerve endings as primary chemoreceptive structures?

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 
The short latency with which intestinal chemosensitive afferent fibers react to appropriate stimuli and the fact that anesthesia of the mucosa abolishes chemosensitivity strongly suggest that the initiation of discharge takes place at the epithelial lining of the intestinal tract (9) and not by stimulating postabsorptive receptors such as portal vein chemoreceptors (1). However, there are several indications that vagal firing is not due to a direct chemical stimulation of the terminals. Thus, in his listing of different possibilities for chemical signal transduction to afferent nerve terminals, Mei (9) indicated that a direct stimulation via the induction of membrane effects by different nutrients is unlikely because it does not account for the specific sensitivity of certain intestinal chemoreceptors (e.g., glucoreceptors and amino acid-sensitive receptors). Also, tracing studies have shown that, in the duodenal mucosa, vagal sensory afferents are in close proximity to the intestinal epithelium but never actually enter the epithelial layer (Ref. 1; Fig. 1). Additional evidence for an indirectly mediated effect of chemical signals is the finding that vagal afferent fibers are stimulated by CCK via CCK-A receptors (see, e.g., Ref. 6). It has been suggested that the hormones may be released from epithelial endocrine cells and act in a paracrine fashion to stimulate vagal afferent terminals in close vicinity (see, e.g., Ref. 1, Fig. 1).

	Involvement of enteroendocrine cells in chemoreception

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 
The latter suggestion leads to the consideration of enteroendocrine cells as primary chemoreceptive elements. At the light microscope level, enteroendocrine cells are conspicuous because of transmitter (or hormone)-containing secretory granules mostly aggregated in the basal cytoplasm (Fig. 1). The different enteroendocrine cell types have been classified according to the shape, size, and contents of their secretory granules. Two groups of enteroendocrine cells can be distinguished according to their epithelial localization: first, the "closed cells" that do not reach the epithelial surface and, second, the "open cells," which project a tuft of apical microvilli into the intestinal lumen (Fig. 1). On the basis of the fact that the latter cell type extends from lumen to basal lamina, and supported by the ultrastructural detection of putative afferent and efferent nerve profiles in the vicinity of the basis of enteroendocrine cells in rat and guinea pig duodenum, it has been suggested that enteroendocrine cells function as chemoreceptive cells (see, e.g., Ref. 1). Further support for this hypothesis comes from the observation that afferent sensory fibers are stimulated by enteroendocrine peptides (see above). However, Richards et al. (11) reported that the CCK sensitivity they detected in some vagal sensory fibers represented only one aspect of the broad chemosensitivity of these mucosal afferents and was not obligatory in this signal transduction pathway. Also, there is little conclusive evidence for a direct interaction of food with endocrine cells resulting in peptide release.

In contrast, an increasing body of evidence indicates that the release of various peptides from enteroendocrine cells in answer to nutrient stimulation is indirectly regulated. Both neural and hormonal (paracrine, endocrine, and luminocrine) mechanisms have been considered as mediators of the regulation. For the best studied of the enteroendocrine cells, the CCK cells, experimental evidence indicates the existence of specific CCK-releasing factors. Two proteins, the luminal cholecystokinin-releasing factor (LCRF) and the monitor peptide, have been purified from rat pancreatic juice and have been shown to be able to stimulate CCK secretion when instilled into the intestine (6). Additionally, the existence of an intestinal luminal releasing factor has been proposed, and the releasing factors are thought to act via putative specific receptors in the luminal membrane of CCK cells (Ref. 6; Fig.1). It appears, therefore, that enteroendocrine cells cannot in general be regarded as "taste cells" of the gut. Because the response of enteroendocrine cells, even if indirectly mediated, is promptly initiated by the ingestion of food, it is feasible that other epithelial cells could fulfil this role. A major structural prerequisite for chemosensory cells is that they have access to the luminal contents of the gut. Of the epithelial cell types that fulfil this precondition, enterocytes and brush cells have repeatedly been implicated in "taste" reception. Because no evidence has as yet been obtained indicating chemoreceptive properties for "clear cells" and for "cup cells," two epithelial cell types restricted to the crypts (clear cells) and villi (cup cells) of the ileum (clear cells supposedly contact mucosal nerve endings), these cell types are not considered further in this review.

	Are enterocytes able to "taste" luminal nutrients?

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 
That enterocytes themselves may possess receptive mechanisms, at least for some types of chemical stimulants, and transmit the signal to sensory afferents was indicated in early experiments that demonstrated discharges of mesenteric nerves related to the active transport of glucose. Nonabsorbed carbohydrates did not initiate discharges, and firing was prevented on addition of phlorizin, a blocker of the Na⁺-glucose cotransporter (SGLT), to the glucose solution (see Ref. 9). Subsequently, it was reported that satiation induced by oligosaccharide perfusion of the intestine was blocked by phlorizin (see Ref. 1). Recent experiments corroborated the suggestion that the rapid accumulation of glucose within enterocytes and/or an activation of SGLT was involved in the regulation of gastrointestinal functions. They showed that intestinal perfusion with glucose, or with a nonmetabolizable glucose analog transported by SGLT, inhibited gastric motility in awake rats, whereas this effect was not reproduced using a nontransportable glucose analog. Blocking of SGLT with phlorizin attenuated the glucose-induced inhibition of gastric motility (10).

Recent findings of our laboratory indicate that enterocytes express a 55-kDa species of rod -transducin that is also the major -transducin form found in taste cells of the tongue (Fig. 2), where transducin appears to be involved in transduction of bitter-tasting molecules such as denatonium (4). Thus, in addition to a possible "glucose tasting" function via the SGLT, the enterocytes may possess further tasting mechanisms of an as yet unknown specificity (Fig. 1).

View larger version (43K): [in this window] [in a new window]   FIGURE 2. Demonstration of -gustducin in a gastric brush cell (A) and of -transducin in enterocytes (B) by immunostaining (A, B) and immunoblotting (C) of rat tissues. Immunoreactivity for -gustducin is concentrated in apical tuft of microvilli (arrow in A). Moderate immunostaining occurs also along basolateral cell surface (arrowhead in A). -Transducin immunostain is absent from brush cells and restricted to apical brush border of enterocytes (B). Immunoblotting of rat gastric mucosa reveals -gustducin at 42 kDa (lane 1). Intestinal epithelium contains a 55-kDa form of -transducin (lane 4) that comigrates with major 55-kDa -transducin form of rat lingual foliate papillae (lane 3). In rat retina (lane 2) antibody detects orthodoxic 39-kDa rod -transducin that is also present as minor form in lingual foliate papillae (lane 3). Bar, 10 µm.

	Are brush cells taste receptor cells of the gut?

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

View larger version (42K): [in this window] [in a new window]   FIGURE 3. Structure and cytoskeletal features of gastrointestinal brush cells. Many of these features are shared by taste cells of the tongue, i.e., long actin filament rootlets extending basally into supranuclear area, abundant microtubules, lateral villin associated with lateral microvilli, and high content of intermediate filaments (CK8/18). In both taste cells and intestinal brush cells, -gustducin is concentrated in apical microvilli but also occurs along basolateral cell surface. Villin associated with lateral cell surface is not found in any other cell type of the intestine but is also seen in taste cells of the tongue.

Immunostaining with anti-gustducin showed that the luminal cell pole of both brush cells and taste receptor cells was the most strongly labeled portion in both cell types (Fig. 2). This portion, with its numerous microvilli, is regarded as the most likely site for chemoreception. In addition, brush cells, like lingual taste receptor cells, contain -gustducin along their basolateral cell surface, opening the possibility that these cells might also sense blood-borne molecules that may modify their receptor function. No other cell type in the gastrointestinal tube reacted with -gustducin antibodies.

More recently, we found that brush cells of the common pancreatic bile duct also contain -gustducin. Because brush cells are extremely abundant in the pancreatic duct (up to 20% of all epithelial cells) and have no contact with the intestinal fluid, it is conceivable that brush cells in the pancreatic system can also sense components of the pancreatic fluid (e.g., the above-mentioned monitor peptide) and may play a role in some aspects of the control of pancreatic secretion.

Thus it appears that both enterocytes and brush cells may be able to perceive luminal chemical signals. In this, they may act mutually exclusively, i.e., each perceives specific signals that the other type cannot recognize. The fact that, at the moment, only carbohydrates are thought to be able to induce chemosensory reactions via enterocytic receptive mechanisms may indicate that other nutrient components are perceived by brush cells, perhaps even by different types of brush cells. On the other hand, it may be a matter of the concentration of the stimulating substances, with lower concentrations being perceived by the specialized cells and higher concentrations by a more general mechanism present in the abundant majority of epithelial cells. These questions, and the possibility of still other cell types being involved in chemosensory perception, remain to be answered.

	Possible mechanisms of how enterocytes and brush cells transmit chemoreceptive signals

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 
Although the findings reported here suggest a chemosensory role for enterocytes and brush cells, the obvious question arises of how the signals are further transduced within the cells and of how they are transmitted to other cells and/or afferent nerve fibers.

It is presently unknown how enterocytic Na⁺-glucose uptake may act as a signal for the suppression of gastrointestinal motility. However, recent identification of nitric oxide (NO) synthase I (NOS I) and NADPH-diaphorase in the gastrointestinal surface epithelium (see, e.g., Ref. 12) offers a possibility of how the epithelial lining of the gut might translate the uptake activity into a signal transmitted to the afferent loop of the chemosensory pathway described here. Glucose-coupled influx of Na⁺ (through SGLT) may stimulate a Na⁺/Ca²⁺ exchange mechanism that would lead to an increase in cytosolic Ca²⁺, which, in turn, would enhance NOS I activity.

NO would be an even more likely candidate for chemosensory signaling in brush cells, because these cells display an extremely strong immunoreactivity for NOS I and for the key enzyme for NADPH production, glucose-6-phosphate dehydrogenase (5). NO, generated from the amino acid arginine by NOS, is a widely spread messenger molecule regulating, e.g., blood vessel dilation or serving as a neurotransmitter in the nervous system. It is tempting to speculate that chemical signals perceived by brush cells and enterocytes are transduced via -gustducin and -transducin, respectively, and that the transduction pathway results in the generation of NO. Specificity of the effects in answer to the different chemical stimuli could be obtained by differential targeting of the NO signal in the mucosa depending on the type and the intestinal localization of cells bearing the putative specific receptors and/or on the amount of NO released. Thus comparatively small amounts of NO released from brush cells might stimulate adjacent enteroendocrine (e.g., CCK cells), absorptive, or secretory cells or exert direct influence on sensory afferents in specific parts of the intestinal mucosa. NO released from enterocytes could produce a "mass effect" on mucosal targets (Fig. 1).

As a local (side) effect, NO might additionally act on smooth muscle cells, blood vessels, or other cell types of the gut wall that, in turn, might indirectly affect sensory afferents by chemical or mechanical stimuli (Fig. 1). Berthoud et al. (1) described particularly intimate associations of vagal afferent nerve fibers with fibrocyte-like cells located just beneath the epithelial lining. These cells resemble intestinal subepithelial myofibroblasts that belong to a family of functionally related cells termed juxtaparenchymal cells (13). Juxtaparenchymal cells are thought to mediate and integrate signaling by soluble mediators or by direct contacts between parenchymal cells and, e.g., endocrine and neural tissue (13). Another intestinal member of this family are the interstitial cells of Cajal, which are postulated to represent smooth muscle pacemakers and mediators of neurotransmission in the gastrointestinal tract. Interstitial cells of Cajal are closely apposed by NOS-immunoreactive nerve endings (8) and show increases in cGMP immunoreactivity on treatment with the NO donor sodium nitroprusside (15). The finding by Valentich et al. (13) that a subepithelial myofibroblast cell line derived from neonatal human colon showed an increased cGMP production in answer to stimulation with atrial natriuretic peptide, but not when treated with NO donor, appears to argue against this proposition. However, Young et al. (15) described "groups of fibroblast-like cells in submucosal preparations of colon" with NO donor-inducible cGMP immunoreactivity. Thus among the subepithelial myofibroblasts there may be more than one type of cell, and another as yet not clearly documented type may be similar to the interstitial cells of Cajal in its ability to respond to NO stimulation. Such cells, then, could represent recipients of the epithelial NO signal and transmit it to the nerve fibers associated with them. Further investigations will have to elucidate whether fibrocyte-like cells contacted by vagal afferent fibers (1) possess characteristics required to fulfil a role as mediators of NO transmission.

Another possible indirect way of NO action on nerve fibers could be via a paracrine stimulation of enteroendocrine cells, followed by release of peptides that then stimulate the afferents (see above, Fig. 1).

	Concluding remarks

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 
The data reviewed in this paper imply that the epithelial lining of the gastrointestinal tube provides primary sites for perception of chemical components of the luminal contents. The chemosensory information must be somehow transmitted to afferent nerve fibers and enteroendocrine cells, both of which are involved in the regulation of the efficiency of gastrointestinal digestion and resorption. It is clear that several primary mechanisms for epithelial perception must exist. Glucose, for instance, must be transported into the cells by SGLT to elicit an adequate chemosensory response. Other substances may be sensed by still-unknown seven transmembrane domain receptors in the luminal plasma membrane that are coupled to taste-specific G proteins such as -gustducin and -transducin. Both G proteins have been demonstrated to be concentrated in the apical membrane of intestinal brush cells (-gustducin) and enterocytes (-transducin). These G proteins might induce intracellular signaling pathways similar to those in lingual taste receptor cells. CCK and NO are likely candidates for signaling between the epithelial lining and afferent nerve endings of the mucosa. To our knowledge, no experiments have been conducted so far elucidating the role of NO in chemoperception. Further progress in our understanding of the primary steps of chemoperception in the gut will probably come from identification of taste receptor molecules of the tongue that might also turn out to be expressed in epithelial cells of the gastrointestinal mucosa.

	References

Top Introduction Neuronal and enteroendocrine... Afferent nerve endings as... Involvement of enteroendocrine... Are enterocytes able to... Are brush cells taste... Possible mechanisms of how... Concluding remarks References

 

1. Berthoud, H. R., M. Kressel, H. E. Raybould, and W. L. Neuhuber. Vagal sensors in the rat duodenal mucosa: distribution and structure as revealed by in vivo DiI-tracing. Anat. Embryol. 191: 203–212, 1995.[Medline]
2. Höfer, D., and D. Drenckhahn. Identification of brush cells in the alimentary and respiratory system by antibodies to villin and fimbrin. Histochemistry 98: 237–242, 1992.[Medline]
3. Höfer, D., B. Püschel, and D. Drenckhahn. Taste receptor-like cells in the gut identified by expression of -gustducin. Proc. Natl. Acad. Sci. USA 93: 6631–6634, 1996.[Abstract/Free Full Text]
4. Kinnamon, S. C., and R. F. Margolskee. Mechanisms of taste transduction. Curr. Opin. Neurobiol. 6: 506–513, 1996.[Medline]
5. Kugler, P., and D. Drenckhahn. Intrinsic source of stomach NO. Nature 370: 25–26, 1994.[Medline]
6. Liddle, R. A. Cholecystokinin cells. Annu. Rev. Physiol. 59: 221–242, 1997.[Medline]
7. Madara, J. L., and J. S. Trier. Functional morphology of the mucosa of the small intestine. In: Physiology of the Gastrointestinal Tract (2nd ed.), edited by L. R. Johnson. New York: Raven, 1987, vol. 2, p. 1209–1249.
8. Matini, P., and M. S. Faussone-Pellegrini. Ultrastructural localization of neuronal nitric oxide synthase-immunoreactivity in the rat ileum. Neurosci. Lett. 229: 45–48, 1997.[Medline]
9. Mei, N. Intestinal chemosensitivity. Physiol. Rev. 65: 211–237, 1985.[Free Full Text]
10. Raybould, H. E., and T. T. Zittel. Inhibition of gastric motility induced by intestinal glucose in awake rats: role of Na(+)-glucose co-transporter. Neurogastroenterol. Motil. 7: 9–14, 1995.[Medline]
11. Richards, W., K. Hillsley, C. Eastwood, and D. Grundy. Sensitivity of vagal mucosal afferents to cholecystokinin and its role in afferent signal transduction in the rat. J. Physiol. (Lond.) 497: 473–481, 1996.[Abstract/Free Full Text]
12. Torihashi, S., B. Horowitz, J. S. Pollok, S. M. Ward, C. Xue, S. Kobayashi, and K. M. Sanders. Expression of nitric oxide synthase in mucosal cells of the canine colon. Histochem. Cell Biol. 105: 33–41, 1996.[Medline]
13. Valentich, J. D., V. Popov, J. I. Saada, and D. W. Powell. Phenotypic characterization of an intestinal subepithelial myofibroblast cell line. Am. J. Physiol. 272 (Cell Physiol. 41): C1513–C1524, 1997.[Abstract/Free Full Text]
14. Walsh, J. H. Gastrointestinal hormones. In: Physiology of the Gastrointestinal Tract (2nd ed.), edited by L. R. Johnson. New York: Raven, 1987, vol. 1, p. 181–253.
15. Young, H. M., K. McConalogue, J. B. Furness, and J. DeVente. Nitric oxide targets in the guinea-pig intestine identified by induction of cyclic GMP immunoreactivity. Neuroscience 55: 583–596, 1993.[Medline]

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