Caged capsaicins: New tools for the examination of TRPV1 channels in somatosensory neurons.
The vanilloid capsaicin, N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide, is the pungent ingredient of chili peppers and is used in pain research as an activating ligand of heat-sensitive transduction channels in nociceptive neurons. Here we describe the synthesis and application of two capsaicin derivatives modified at the hydroxy function of the vanillyl motif: alpha-carboxy-4,5-dimethoxy-2-nitrobenzyl-caged (CDMNB-caged) capsaicin and {7-[bis(carboxymethyl)amino]coumarin-4-yl}methoxycarbonyl-caged (BCMACMOC-caged) capsaicin. These compounds show dramatically reduced pungency, but release active capsaicin upon irradiation with UV light. CDMNB-caged capsaicin can be used to perform concentration-jump experiments, while BCMACMOC-caged capsaicin is membrane-impermeant and can be applied selectively to the intracellular or extracellular sides of a plasma membrane. Both compounds can serve as valuable research tools in pain physiology.
Gilbert
Daniel
D
Department of Molecular Physiology, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.
Funk
Katharina
K
Dekowski
Brigitte
B
Lechler
Ralf
R
Keller
Sandro
S
Möhrlen
Frank
F
Frings
Stephan
S
Hagen
Volker
V
D000818:Animals; D001593:Benzyl Compounds / Q000737:chemistry*; D001671:Biochemistry / Q000295:instrumentation / Q000379:methods; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy; D021381:Protein Transport; D051381:Rats; D050916:TRPV Cation Channels / Q000737:chemistry / Q000502:physiology*; D014466:Ultraviolet Rays
D001593:Benzyl Compounds; D008024:Ligands; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C518785:alpha-carboxy-4,5-dimethoxy-2-nitrobenzyl capsaicin; D002211:Capsaicin