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Voltage-dependent modulation of TRPA1 currents by diphenhydramine
Xianfeng Shen1, Qiaochu Wang2, Yakang Lin3
1Department of Hepatobiliary Pancreatic Medical Center, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, PR China.
Cell Calcium
|July 8, 2020
Summary
Diphenhydramine (DPH) modulates the TRPA1 channel, affecting itch and pain signaling. This antihistamine enhances inward currents while suppressing outward currents, suggesting a novel therapeutic mechanism.
Area of Science:
- Neuroscience
- Pharmacology
- Ion Channel Physiology
Background:
- Diphenhydramine (DPH) is widely used for allergies and topical relief of itching and pain.
- The transient receptor potential ankyrin 1 (TRPA1) channel is implicated in acute and chronic itch and pain.
- The effect of DPH on TRPA1 channel activity was previously unknown.
Purpose of the Study:
- To investigate whether diphenhydramine (DPH) affects the activity of the TRPA1 channel.
- To elucidate the mechanism by which DPH might exert its therapeutic effects on itch and pain.
Main Methods:
- Whole-cell patch clamp recordings were utilized to measure ion channel activity.
- TRPA1 and TRPV1 channels were activated by specific agonists.
- The voltage-dependence of channel currents was analyzed in the presence and absence of DPH.
Main Results:
- Diphenhydramine (DPH) significantly modulated the voltage-dependence of TRPA1 channels.
- DPH enhanced inward currents and suppressed outward currents of TRPA1, causing inward rectification.
- This modulation occurred with various TRPA1 agonists, across species, and in a specific TRPA1 mutant, suggesting multiple interaction sites. DPH also partially blocked capsaicin-evoked TRPV1 currents.
Conclusions:
- Diphenhydramine (DPH) alters TRPA1 channel function in a voltage-dependent manner.
- These findings suggest that DPH's therapeutic effects on itch and pain may involve the modulation of TRPA1.
- DPH may also interact with TRPV1 channels, contributing to its analgesic properties.
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