Lipophilicity of capsaicinoids and capsinoids influences the multiple activation process of rat TRPV1.
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.
Morita
Akihito
A
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
Iwasaki
Yusaku
Y
Kobata
Kenji
K
Iida
Tohko
T
Higashi
Tomohiro
T
Oda
Kyoko
K
Suzuki
Asami
A
Narukawa
Masataka
M
Sasakuma
Shiho
S
Yokogoshi
Hidehiko
H
Yazawa
Susumu
S
Tominaga
Makoto
M
Watanabe
Tatsuo
T
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*
D018712:Analgesics, Non-Narcotic; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002211:Capsaicin; D002118:Calcium