Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal
Beteiligte:
Li Puma, Simone;
Landini, Lorenzo;
Macedo, Sergio J.;
Seravalli, Viola;
Marone, Ilaria M.;
Coppi, Elisabetta;
Patacchini, Riccardo;
Geppetti, Pierangelo;
Materazzi, Serena;
Nassini, Romina;
De Logu, Francesco
Erschienen:
Wiley, 2019
Erschienen in:Journal of Cellular and Molecular Medicine
Sprache:
Englisch
DOI:
10.1111/jcmm.14099
ISSN:
1582-1838;
1582-4934
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Safranal, contained in <jats:italic>Crocus sativus</jats:italic> L., exerts anti‐inflammatory and analgesic effects. However, the underlying mechanisms for such effects are poorly understood. We explored whether safranal targets the transient receptor potential ankyrin 1 (<jats:styled-content style="fixed-case">TRPA</jats:styled-content>1) channel, which in nociceptors mediates pain signals. Safranal by binding to specific cysteine/lysine residues, stimulates <jats:styled-content style="fixed-case">TRPA</jats:styled-content>1, but not the <jats:styled-content style="fixed-case">TRP</jats:styled-content> vanilloid 1 and 4 channels (<jats:styled-content style="fixed-case">TRPV</jats:styled-content>1 and <jats:styled-content style="fixed-case">TRPV</jats:styled-content>4), evoking calcium responses and currents in human cells and rat and mouse dorsal root ganglion (<jats:styled-content style="fixed-case">DRG</jats:styled-content>) neurons. Genetic deletion or pharmacological blockade of <jats:styled-content style="fixed-case">TRPA</jats:styled-content>1 attenuated safranal‐evoked release of calcitonin gene‐related peptide (<jats:styled-content style="fixed-case">CGRP</jats:styled-content>) from rat and mouse dorsal spinal cord, and acute nociception in mice. Safranal contracted rat urinary bladder isolated strips in a <jats:styled-content style="fixed-case">TRPA</jats:styled-content>1‐dependent manner, behaving as a partial agonist. After exposure to safranal the ability of allyl isothiocyanate (<jats:styled-content style="fixed-case">TRPA</jats:styled-content>1 agonist), but not that of capsaicin (<jats:styled-content style="fixed-case">TRPV</jats:styled-content>1 agonist) or <jats:styled-content style="fixed-case">GSK</jats:styled-content>1016790A (<jats:styled-content style="fixed-case">TRPV</jats:styled-content>4 agonist), to evoke currents in <jats:styled-content style="fixed-case">DRG</jats:styled-content> neurons, contraction of urinary bladder strips and <jats:styled-content style="fixed-case">CGRP</jats:styled-content> release from spinal cord slices in rats, and acute nociception in mice underwent desensitization. As previously shown for other herbal extracts, including petasites or parthenolide, safranal might exert analgesic properties by partial agonism and selective desensitization of the <jats:styled-content style="fixed-case">TRPA</jats:styled-content>1 channel.</jats:p>