10 0 - EleA@UniSA - Università degli Studi di Salerno

TRPA1 is rendered insensitive to these agonists when specific covalent
acceptor sites are substituted with non reactive residues.
In fact both polygodial and isovelleral have been tested on these TRPA1
mutants and these mutants were totally insensitive to progressive addition of
agonists.
Seems that C-terminus is a critical modulatory domain for TRPA1 activation,
and this end-tail is rich in Lys residue, 46 that means might be possible the
hypothesis of Sodano and co workers that in chemoreception could be involved
a reaction between a Lys and the -unsaturated dialdehydic moiety.
Recently it has been shown that oleocanthal (Figure 1.28) a phenolic
compound isolated by extra virgin oil 47 having an unsaturated dialdehydic
moiety, is able to activate TRPA1 receptor.(Figure 1.33)
HO
1.51
O
O
FIGURE 1.33
This compound, synthesised by Amos Smith III and co-workers, 48 has been
implicated in the bitterness, pungency, and astringency of extra virgin olive oil
and shows inhibitory activities COX-1 and COX-2 , similar in potency to the
NSAID ibuprofen. 49
The irritant effect of oleocanthal is especially in the throat and this is in contrast
with other oral irritants such as cynnamaldehyde, capsaicin which irritate mucus
membranes throughtout the oral cavity.
46
Abdul Samad, Lucie Sura, Jan Benedikt, Rudiger Ettrich, Babak Minofar, Jan Teisinger And Viktorie
Vlachova Biochem. J. (2011) 433, 197–204.
47
Andrewes P, Busch JL, de Joode T, Groenewegen A, Alexandre H. J Agric Food Chem 2003, 51,1415–
1420.
48 Amos B. Smith, III,* Jeffrey B. Sperry, and Qiang Han J. Org. Chem. 2007, 72, 6891-6900
49 Beauchamp, G.; Keast, R.; Morel, D.; Liu, J.; Pika, J.; Han, Q.; Lee, C.; Smith, A. B., III; Breslin, P. Nature
2005, 437, 45-46.
O
O
CH 3
48