Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions

Members of the transient receptor potential (TRP) family of nonselective cation channels are involved in several pathological and physiological conditions. The search for the molecular targets for naturally occurring substances, especially from plants, allowed the characterization of many TRP channels. In fact, attempts to understand the hot and painful action of the vanillyl group containing compounds capsaicin (from Capsicum sp.) and its ultrapotent analogue resiniferatoxin (RTX, from Euphorbia sp.) led to the cloning of the vanilloid receptor (TRPV1) 7 years ago. TRPV1 is found in sensory fibers and functions as a molecular integrator of several painful stimuli, being especially stimulated during inflammation. Since TRPV1 is involved in several pathological conditions, selective ligands or modulators of this channel are substances of potential interest to treat such diseases. Once again, natural products seem to be also interesting sources of compounds that might be prototype TRPV1 ligands. The cloning of TRPV1 also enabled the discovery of other members of the TRPV family of channels. Similar to TRPV1, these receptors function as molecular detectors of physical and chemical stimuli, such as innocuous and noxious heat, as well as mechanical force. Recently, novel TRP channels sensitive to low temperatures also have been cloned, namely, TRPM8 and TRPA1. Such channels are also activated by naturally occurring substances but knowledge of their involvement in health and disease is in its infancy. In the present review, we focused on the contribution of natural products to the discovery of TRP channels and to the development of novel drugs to treat pathological conditions in which these channels are involved.