The cornucopia of intestinal chemosensory transduction

Abstract

The chemosensory transduction mechanisms that the gastrointestinal (GI) tract uses to detect chemical and nutrient stimuli are poorly understood. The GI tract is presented with a wide variety of stimuli including potentially harmful chemicals or toxins as well as 'normal' stimuli including nutrients, bacteria and mechanical forces. Sensory transduction is at its simplest the conversion of these stimuli into a neural code in afferent nerves. Much of the information encoded is used by the enteric nervous system to generate local reflexes while complementary information is sent to the central nervous system via afferents or by release of hormones to affect behaviour. This review focuses on the chemosensory transduction mechanisms present in the GI tract. It examines the expression and localisation of the machinery for chemosensory transduction. It summarises the types of cells which might be involved in detecting stimuli and releasing neuroactive transmitters. Finally, it highlights the idea that chemosensory transduction mechanisms in the GI tract utilise many overlapping and complementary mechanisms for detecting and transducing stimuli into reflex action.

Keywords: chemosensory; enterochromaffin cell; gastrointestinal tract; sensory transduction; serotonin.

Figure 1

Side view of the intestinal wall showing a villus/crypt unit. A diagram showing a section of intestine with a villus/crypt unit shown in detail. The mucosal epithelium (EPI) contains the enterocytes and the enteroendocrine (EE) cells – specialised epithelial cells that contain neuroactive substances located in secretory granules. Several types of EE cell are depicted (different colours) including the 5-HT containing enterochromaffin (EC) cell (depicted releasing 5-HT near to afferent nerve terminals into the underlying lamina propria). Afferent nerve terminals are from extrinsic sources (vagal and dorsal root ganglia) and from intrinsic sources (myenteric and submucosal afferent/sensory neurons).

Figure 2

Nutrients may have two distinct routes to active nerve terminals. A diagram showing a epithelial cells (either side) and an enteroendocrine (EE) cell. Nutrients present in the lumen of the intestine (depicted as star-shapes) may signal to afferent nerve terminals into the underlying lamina propria by two different routes. (A) Stimulants may be ferried across the epithelium by specific transport proteins where they then interact with specialised receptors on the nerve terminals. (B) Receptors and transduction machinery may exist on the luminal aspect of specialised epithelial cells within the mucosal epithelium.

Figure 3

Sensory transduction machinery and the enteroendocrine (EE) cell. A diagram showing an enteroendocrine (EE) cell with machinery. 1. Some of the more important components of the taste transduction machinery are the taste receptors, T1Rs which respond to sweet an umami tastants, and T2Rs which responds to bitter tastants. Receptors for olfactory receptors as well as others exist. 2. These receptors couple to the taste G-protein (gustducin, or in some cases transducin). 3. These in turn couple to taste specific second messenger systems such as phospholipase Cβ2 (PLCβ2). 4. PLCβ2 generates second messengers such as diacylglycerol which can activate specialised ion channel receptors like transient receptor potential ion channel M5 (TRPM5) which is required for the transduction of bitter, sweet and umami tastes. 5. Second messengers such as inositol triphosphate are also generated and can release calcium (Ca⁺⁺) from intracellular stores and causes transmitter release and nerve terminal activation.