TRPV1 Is Activated by Both Acidic and Basic pH

被引：171

作者：

Dhaka, Ajay ^{[1
]}

Uzzell, Valerie ^{[1
]}

Dubin, Adrienne E. ^{[1
]}

Mathur, Jayanti ^{[2
]}

Petrus, Matt ^{[2
]}

Bandell, Michael ^{[2
]}

Patapoutian, Ardem ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA

[2] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 01期

基金：

美国国家卫生研究院;

关键词：

TRPA1; TRPV1; ammonia; nociception; alkalization; pH; COVALENT MODIFICATION; CAPSAICIN RECEPTOR; GANGLION NEURONS; INTRACELLULAR PH; PAIN SENSATION; ION CHANNELS; TRPA1; SENSITIVITY; NOCICEPTION; DETERMINES;

D O I：

10.1523/JNEUROSCI.4901-08.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Maintaining physiological pH is required for survival, and exposure to alkaline chemicals such as ammonia (smelling salts) elicits severe pain and inflammation through unknown mechanisms. TRPV1, the capsaicin receptor, is an integrator of noxious stimuli including heat and extracellular acidic pH. Here, we report that ammonia activates TRPV1, TRPA1 (another polymodal nocisensor), and other unknown receptor(s) expressed in sensory neurons. Ammonia and intracellular alkalization activate TRPV1 through a mechanism that involves a cytoplasmic histidine residue, not used by other TRPV1 agonists such as heat, capsaicin or low pH. Our studies show that TRPV1 detects both acidic and basic deviations from homeostatic pH.

引用

页码：153 / 158

页数：6

共 23 条

[1] Impaired nociception and pain sensation in mice lacking the capsaicin receptor [J].

Caterina, MJ ;

Leffler, A ;

Malmberg, AB ;

Martin, WJ ;

Trafton, J ;

Petersen-Zeitz, KR ;

Koltzenburg, M ;

Basbaum, AI ;

Julius, D .

SCIENCE, 2000, 288 (5464) :306-313

[2] Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality [J].

Ciura, Sorana ;

Bourque, Charles W. .

JOURNAL OF NEUROSCIENCE, 2006, 26 (35) :9069-9075

[3] TRP ion channels and temperature sensation [J].

Dhaka, Ajay ;

Viswanath, Veena ;

Patapoutian, Ardem .

ANNUAL REVIEW OF NEUROSCIENCE, 2006, 29 :135-161

[4]

FLURY KE, 1983, MAYO CLIN PROC, V58, P389

[5] Intracellular alkalization causes pain sensation through activation of TRPA1 in mice [J].

Fujita, Fumitaka ;

Uchida, Kunitoshi ;

Moriyama, Tomoko ;

Shima, Asako ;

Shibasaki, Koji ;

Inada, Hitoshi ;

Sokabe, Takaaki ;

Tominaga, Makoto .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (12) :4049-4057

[6] AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties [J].

Gavva, NR ;

Tamir, R ;

Qu, YS ;

Klionsky, L ;

Zhang, TJ ;

Immke, D ;

Wang, J ;

Zhu, D ;

Vanderah, TW ;

Porreca, F ;

Doherty, EM ;

Norman, MH ;

Wild, KD ;

Bannon, AW ;

Louis, JC ;

Treanor, JJS .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 313 (01) :474-484

[7] TRP channel activation by reversible covalent modification [J].

Hinman, Andrew ;

Chuang, Huai-hu ;

Bautista, Diana M. ;

Julius, David .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (51) :19564-19568

[8] Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel [J].

Kirichok, Y ;

Navarro, B ;

Clapham, DE .

NATURE, 2006, 439 (7077) :737-740

[9] Modulation of N-type Ca2+ channels by intracellular pH in chick sensory neurons [J].

Kiss, L ;

Korn, SJ .

JOURNAL OF NEUROPHYSIOLOGY, 1999, 81 (04) :1839-1847

[10] TRPA1 contributes to cold, mechanical, and chemical Nociception but is not essential for hair-cell transduction [J].

Kwan, KY ;

Allchorne, AJ ;

Vollrath, MA ;

Christensen, AP ;

Zhang, DS ;

Woolf, CJ ;

Corey, DP .

NEURON, 2006, 50 (02) :277-289

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