TRP Channel Related Drug Discovery Products

In a variety of cell types, including neurons, transient receptor potential (TRP) channels are widely expressed on the plasma membrane. TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), TRPML (mucolipin), and TRPN (Drosophila NOMPC) are the seven TRP families. It is challenging to distinguish the functions of each family and member just based on the classification of the TRP superfamily, which is based on distinctions in their amino acid sequences and topological structures. TRPs actually respond to a wide range of extracellular and intracellular inputs by acting in a variety of healthy and pathological ways. TRP channels, which can have homo- or hetero-tetrameric topologies, integrate several signaling pathways once they are active to cause a series of reactions. Six putative transmembrane spanning domains with intracellular C and N termini and a porelining between the fifth and sixth transmembrane domains are shared structural characteristics of TRPs. Creative Biolabs can offer TRP channel related products to contribute to the success of drug discovery.

Overview of TRP Channel

• TRPV

TRPV1, TRPV2, TRPV3, and TRPV4 are thermo-TRP channels that are activated by vanillin, vanillic acid, and capsaicin in plants because they can be triggered by heat. There are six unique members of TRPV family (TRPV1-6). In contrast to TRPV1-4, which are known as nocireceptors that perceive the damaging impulses, TRPV5 and TRPV6 are epithelial calcium ion channels.

Fig.1. Structural domains and motifs of TRPV channels.¹

• TRPA

Because TRPA has several N-terminal ankyrin repeats, it was originally given the moniker ANKTM1. Mammals only have one TRPA family member, TRPA1, as opposed to the two and four TRPA members seen in C. elegans and Drosophila, respectively.Painful cold with a temperature lower than 17 °C activates TRPA1. The pain-detecting sensory nerves' plasma membranes contain TRPA1, which activates pathways that cause avoidance behavior as well as pathways that support long-lasting reactions like inflammation. Therefore, blocking TRPA1 function is an effective way to lessen discomfort.

Fig.2. Structural domains and motifs of TRPA channels.¹

• TRPC

The TRPC family and the TRP channel family from Drosophila are most similar. There are seven members of the TRPC family (TRPC1–7), with TRPC2 being a pseudogene in people. The N-terminal 750–900 amino acids of the seven mammalian homologs are 30% identical. The mammalian TRPCs can be divided into four subsets based on sequence alignments and functional comparisons: TRPC1, TRPC2, TRPC3/6/7, TRPC4/5 and TRPC4.

Fig.3. Structural domains and motifs of TRPC channels.¹

• TRPM

Mammals have eight members of the TRPM family (TRPM1–8). TRPMs can be divided into three subgroups based on sequence homology: TRPM1-3, TRPM4-5, and TRPM6-7. On intracellular membranes, TRPMs are found in some instances.

Fig.4. Structural domains and motifs of TRPM channels.¹

References

1. Méndez-Reséndiz, Karina Angélica, et al. "Steroids and TRP channels: a close relationship." International Journal of Molecular Sciences 21.11 (2020): 3819.
   Distributed under Open Access license CC BY 4.0, selected a part of original Figure 2.