title: Lipophilicity of capsaicinoids and capsinoids influences the multiple activation process of rat TRPV1.
abstract: Analogs of capsaicin, such as capsaicinoids and capsinoids, activate a cation channel, transient receptor potential cation channel vanilloid subfamily 1 (TRPV1), and then increase the intracellular calcium concentration ([Ca2+]i). These compounds would be expected to activate TRPV1 via different mechanism(s), depending on their properties. We synthesized several capsaicinoids and capsinoids that have variable lengths of acyl moiety. The activities of these compounds towards TRPV1 heterologously expressed in HEK293 cells were determined by measuring [Ca2+]i. When an extracellular or intracellular Ca2+ source was removed, some agonists such as capsaicin could increase [Ca2+]i. However, a highly lipophilic capsaicinoid containing C18:0 and capsinoids containing C14:0, C18:0, or C18:1 (the latter was named olvanilate) could not elicit a large increase in [Ca2+]i in the absence of an extracellular or intracellular Ca2+ source. These results suggest that highly lipophilic compounds cause only a slight Ca2+ influx, via TRPV1 in the plasma membrane, and are not able to activate TRPV1 in the endoplasmic reticulum.
authors.affiliation: School of Food and Nutritional Sciences and COE Program in the 21st Century, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. moritaa@u-shizuoka-ken.ac.jp
authors.forename: Akihito
authors.initials: A
authors.lastname: Morita
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobata
authors.forename: Tohko
authors.initials: T
authors.lastname: Iida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Higashi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Oda
authors.forename: Asami
authors.initials: A
authors.lastname: Suzuki
authors.forename: Masataka
authors.initials: M
authors.lastname: Narukawa
authors.forename: Shiho
authors.initials: S
authors.lastname: Sasakuma
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Yokogoshi
authors.forename: Susumu
authors.initials: S
authors.lastname: Yazawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D012995:Solubility; D050916:TRPV Cation Channels / Q000096:biosynthesis*
chemical_list: D018712:Analgesics, Non-Narcotic; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002211:Capsaicin; D002118:Calcium