Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters

Phthalic acid (PA) diesters are widely used in consumer products, as plasticizers, and are ubiquitous environmental pollutants. There is a growing concern about their adjuvant effect on allergic diseases. Although its precise mechanism remains unknown, possible involvement of transient receptor pote...

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Bibliographic Details
Published inBiological & pharmaceutical bulletin Vol. 45; no. 12; pp. 1839 - 1846
Main Authors Mori, Yoko, Aoki, Akira, Okamoto, Yoshinori, Isobe, Takashi, Ohkawara, Susumu, Hanioka, Nobumitsu, Tanaka-Kagawa, Toshiko, Jinno, Hideto
Format Journal Article
LanguageEnglish
Published Tokyo The Pharmaceutical Society of Japan 01.12.2022
Japan Science and Technology Agency
Subjects
adjuvant effect
Allergic diseases
Ankyrins
Esters
nociceptive receptor
Phthalic acid
phthalic acid ester
species difference
transient receptor potential ankyrin 1
Transient receptor potential proteins
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Summary:Phthalic acid (PA) diesters are widely used in consumer products, as plasticizers, and are ubiquitous environmental pollutants. There is a growing concern about their adjuvant effect on allergic diseases. Although its precise mechanism remains unknown, possible involvement of transient receptor potential ankyrin 1 (TRPA1) has been suggested. Hence, in this study, the activation of human and mouse TRPA1s by a series of PA di- and monoesters was investigated using a heterologous expression system in vitro. Consequently, it was found that monoesters activated human TRPA1, where EC50 values were in the order of mono-hexyl > mono-heptyl > mono-n-octyl > mono-2-ethylhexyl > mono-isononyl and mono-isodecyl esters. Significant species differences in TRPA1 activation by PA monoesters were also discovered; PA monoesters activated human TRPA1 but not mouse TRPA1 in a concentration-dependent manner up to 50 µM. These findings suggest that PA esters may exert TRPA1-dependent adverse effects on humans, which have never been demonstrated in experimental animals.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b22-00645