Production of a specific extracellular inhibitor of TRPM3 channels

Background and purpose: Isoform‐specific ion channel blockers are useful for target validation in drug discovery and can provide the basis for new therapeutic agents and aid in determination of physiological functions of ion channels. The aim of this study was to generate a specific blocker of human...

Full description

Saved in:
Bibliographic Details
Published in:British journal of pharmacology 2008-10, Vol.155 (4), p.567-573
Main Authors: Naylor, J, Milligan, C J, Zeng, F, Jones, C, Beech, D J
Format: Article
Language:English
Subjects:
Antibodies - pharmacology
antibody
Biological and medical sciences
Calcium - metabolism
calcium channel
cation channel
Cell Line
Fluorescent Dyes
Fura-2 - metabolism
Humans
Kidney - metabolism
Medical sciences
Patch-Clamp Techniques - methods
Pharmacology. Drug treatments
Protein Binding
Research Papers
transient receptor potential
TRPM Cation Channels - antagonists & inhibitors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background and purpose: Isoform‐specific ion channel blockers are useful for target validation in drug discovery and can provide the basis for new therapeutic agents and aid in determination of physiological functions of ion channels. The aim of this study was to generate a specific blocker of human TRPM3 channels as a tool to help investigations of this member of the TRP cationic channel family. Experimental approach: A polyclonal antibody (TM3E3) was made to a conserved peptide of the third extracellular (E3) loop of TRPM3 and tested for binding and functional effect. Studies of channel activity were made by whole‐cell planar patch‐clamp and fura‐2 intracellular Ca2+ measurement. Key results: Ionic current mediated by TRPM3 was inhibited partially by TM3E3 over a period of 5–10 min. Ca2+ entry in TRPM3‐expressing cells was also partially inhibited by TM3E3 in a peptide‐specific manner and independently of the type of agonist used to activate TRPM3. TM3E3 had no effect on TRPC5, TRPV4, TRPM2 or an endogenous ATP response. Conclusions and implications: The data show the successful development of a specific TRPM3 inhibitor and give further confidence in E3 targeting as an approach to producing isoform‐specific ion channel blockers. British Journal of Pharmacology (2008) 155, 567–573; doi:10.1038/bjp.2008.283; published online 7 July 2008
ISSN:0007-1188
1476-5381
DOI:10.1038/bjp.2008.283