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TRP Modulation by Natural Compounds

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Mammalian Transient Receptor Potential (TRP) Cation Channels

Abstract

The use of medicinal plants or other naturally derived products to relieve illness can be traced back over several millennia, and these natural products are still extensively used nowadays. Studies on natural products have, over the years, enormously contributed to the development of therapeutic drugs used in modern medicine. By means of the use of these substances as selective agonists, antagonists, enzyme inhibitors or activators, it has been possible to understand the complex function of many relevant targets. For instance, in an attempt to understand how pepper species evoke hot and painful actions, the pungent and active constituent capsaicin (from Capsicum sp.) was isolated in 1846 and the receptor for the biological actions of capsaicin was cloned in 1997, which is now known as TRPV1 (transient receptor potential vanilloid 1). Thus, TRPV1 agonists and antagonists have currently been tested in order to find new drug classes to treat different disorders. Indeed, the transient receptor potential (TRP) proteins are targets for several natural compounds, and antagonists of TRPs have been synthesised based on the knowledge of naturally derived products. In this context, this chapter focuses on naturally derived compounds (from plants and animals) that are reported to be able to modulate TRP channels. To clarify and make the understanding of the modulatory effects of natural compounds on TRPs easier, this chapter is divided into groups according to TRP subfamilies: TRPV (TRP vanilloid), TRPA (TRP ankyrin), TRPM (TRP melastatin), TRPC (TRP canonical) and TRPP (TRP polycystin). A general overview on the naturally derived compounds that modulate TRPs is depicted in Table 1.

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Abbreviations

ADP:

Adenosine monophosphate

ADPDK:

Polycystic kidney disease

Akt:

v-Akt murine thymoma viral oncogene

CAMKIV:

Calcium/calmodulin-dependent protein kinase type IV

CGRP:

Calcitonin gene-related peptide

CHO:

Chinese hamster ovary

CREB:

cAMP-responsive element binding protein

DRG:

Dorsal root ganglion

HEK293:

Human embryonic kidney 293

hTM:

Human transmembrane domain

mTM:

Mouse transmembrane domain

ICK:

Inhibitor cysteine knot

nAChRs:

Nicotinic acetylcholine receptor

PI3K:

Phosphoinositide 3-Kinase

PKD:

Protein kinase D

PLC:

Phospholipase C

TG:

Trigeminal ganglion

THC:

Δ9-tetrahydrocannabinol

TRP:

Transient receptor potential

TRPA:

TRP ankyrin

TRPC:

TRP canonical

TRPM:

TRP melastatin

TRPP:

TRP polycystin

TRPV:

TRP vanilloid

VaTx:

Vanillotoxins

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Meotti, F.C., Lemos de Andrade, E., Calixto, J.B. (2014). TRP Modulation by Natural Compounds. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-05161-1_19

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