TRP channels in the digestive system

Abstract

Several of the 28 mammalian transient receptor potential (TRP) channel subunits are expressed throughout the alimentary canal where they play important roles in taste, chemo- and mechanosensation, thermoregulation, pain and hyperalgesia, mucosal function and homeostasis, control of motility by neurons, interstitial cells of Cajal and muscle cells, and vascular function. While the implications of some TRP channels, notably TRPA1, TRPC4, TRPM5, TRPM6, TRPM7, TRPV1, TRPV4, and TRPV6, have been investigated in much detail, the understanding of other TRP channels in their relevance to digestive function lags behind. The polymodal chemo- and mechanosensory function of TRPA1, TRPM5, TRPV1 and TRPV4 is particularly relevant to the alimentary canal whose digestive and absorptive function depends on the surveillance and integration of many chemical and physical stimuli. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 appear to be essential for the absorption of Ca(2+) and Mg(2+), respectively, while TRPM7 appears to contribute to the pacemaker activity of the interstitial cells of Cajal, and TRPC4 transduces smooth muscle contraction evoked by muscarinic acetylcholine receptor activation. The implication of some TRP channels in pathological processes has raised enormous interest in exploiting them as a therapeutic target. This is particularly true for TRPV1, TRPV4 and TRPA1, which may be targeted for the treatment of several conditions of chronic abdominal pain. Consequently, blockers of these TRP channels have been developed, and their clinical usefulness has yet to be established.

Figure 1

Dual functional implications of TRP-expressing abdominal afferent neurons. Following stimulation via activation of TRP channels, afferent nerve fibres release neuropeptides from their peripheral endings, whereby they regulate vascular function, secretory processes, mucosal homeostasis and motor activity. Through their afferent function, TRP-expressing neurons contribute to chemosensation, mechanosensation, thermosensation, pain and hyperalgesia and elicit autonomic reflexes.

Figure 2

Schematic diagram illustrating 3 different roles of TRP channels in the digestive system: (i) their role as molecular sensors (detectors or primary transducers) of chemical and physical stimuli, (ii) their role as downstream or secondary transducers (effectors) of cell activation induced by G protein-coupled receptors or other ion channels, and (iii) their role as ion transport channels.