Differential effects of acute hypoxia on the activation of TRPV1 by capsaicin and acidic pH.
Transient receptor potential vanilloid 1 (TRPV1) is a Ca(2+)-permeable cation channel activated by a variety of physicochemical stimuli. The effect of hypoxia (P(O(2)), 3%) on rat TRPV1 overexpressed in HEK293T has been studied. The basal TRPV1 current (I (TRPV1)) was partly activated by hypoxia, whereas capsaicin-induced TRPV1 (I (TRPV1,Cap)) was attenuated. Such changes were also suggested from hypoxia- and capsaicin-induced Ca(2+) signals in TRPV1-expressing cells. Regarding plausible changes of reactive oxygen species (ROS) under hypoxia, the effects of antioxidants, vitamin C and tiron, as membrane-impermeable and -permeable, respectively, were tested. Both I (TRPV1) and I (TRPV1,Cap) were increased by vitamin C, while only I (TRPV1) was slightly increased by tiron. The hypoxic inhibition of I (TRPV1,Cap) was still persistent under hypoxia/vitamin C. Interestingly, hypoxia/tiron strongly inhibited both I (TRPV1) and I (TRPV1,Cap). Also, with vitamin C applied through a pipette solution, hypoxia inhibited I (TRPV1) and I (TRPV1,Cap). In contrast, hypoxia and hypoxia/tiron had no effect on the I (TRPV1) induced by acid (pH 6.2, I (TRPV1,Acid)). Taken together, hypoxia partly activated TRPV1 while it decreased their sensitivity to capsaicin. Putative changes of ROS under hypoxia might underlie the side-specific effects of ROS on TRPV1: inhibitory at the extracellular and stimulatory at the intracellular side, respectively. The differential effects of hypoxia on I (TRPV1,Cap) and I (TRPV1,Acid) suggested that the intracellular ROS increase might attenuate the pharmacological potency of capsaicin.
Department of Physiology, Seoul National University College of Medicine, Jongnogu, Seoul 110-799, Korea.
Kyung Soo
KS
Kim
Hae Young
HY
Yoo
Kyung Sun
KS
Park
Jin Kyoung
JK
Kim
Yin-Hua
YH
Zhang
Sung Joon
SJ
Kim
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology*; D055724:Electrophysiological Phenomena; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D002211:Capsaicin