How does the intestine taste?

Abstract

There are similarities between the mechanisms of sensory transduction by chemoreceptors in the gastrointestinal (GI) tract and by those in the oral cavity. Dissociated rat taste receptor cells have been shown to contain vesicular 5-HT and are excited by exogenous application of 5-HT. Likewise, in the GI tract, enterochromaffin (EC) cells are well known to contain 5-HT and are excited by its exogenous application. Both the taste receptor cell and the EC cell apparently make reciprocal synaptic connections with their extrinsic and (in the case of the gut) intrinsic afferent innervation. However, while the taste receptor cell is known to participate in gustation, the EC cell's role in the initiation of enteric reflexes remains unclear. Thus it may be that common transduction mechanisms are utilized in both systems and it is in this sense that the gut may be said to 'taste' the contents of the lumen. These studies were designed to investigate the sensory transduction mechanisms underlying responses of myenteric sensory neurons to chemical stimulation of the mucosa and with particular attention to the possible interactions between the EC cell and the surrounding afferent innervation. Intracellular electrophysiological recordings were taken from chemosensory myenteric neurons which had AH type electrophysiological characteristics and Dogiel type II morphological characteristics. Short segments of guinea pig ileum were dissected to reveal the myenteric plexus over one half the circumference of the preparation. Focal stimulating electrodes and fine glass pipettes containing chemical substances were used to stimulate the mucosa in the intact half of the preparation. Movement of the smooth muscle was reduced with the addition of scopolamine and nicardipine. In general, stimulation of the mucosa generated bursts of one or more action potentials (APs) recorded at the cell soma. Puffs of 5-HT (3 - 30 M) or 2-methyl 5-HT (0.1 to 1 mM - a 5-HT3 agonist) applied locally to the mucosa were effective in eliciting bursts of APs while puffs of -methyl 5-HT (0.1 to 1 mM - a 5-HT2 agonist) or 5-methoxytryptamine (1 to 10 M - a general 5-HT agonist) were not. Single, electrical stimuli applied to the mucosa elicited a single antidromic AP and a later burst of APs. Spontaneous bursts of APs were also recorded in some cells which were indistinguishable from the electrically evoked late burst of APs. In one instance, initiation of an antidromic AP by electrical stimulation of the mucosa or a single AP by somatic current injection elicited a late AP which appeared to be the result of synaptic interaction at or near the nerve terminal in the mucosa. In cells with spontaneous bursts of APs or where 5-HT elicited a burst of APs, application of tropisetron (10 M - 5-HT3/4 antagonist) reduced the occurrence of bursts and/or the number of APs in a burst. The electrically evoked late burst of APs was only blocked by higher concentrations of tropisetron (30 M) and was not desensitized during repeated applications of 5-HT to the mucosa. The early, antidromic AP was never blocked. In preliminary experiments, granisetron (10 M - 5-HT3 antagonist) reduced the number of APs in response to 5-HT but not to electrical stimulation. These results are consistent with the idea that 5-HT participates in chemosensory transduction, but also suggest that other substances may play a similar role. In addition, anecdotal evidence suggest that the mucosa and its afferent innervation can interact in a positive, reciprocal fashion.