Influence of Cold-TRP Receptors on Cold-Influenced Behaviour

The transient receptor potential (TRP) channels, TRPA1 and TRPM8, are thermo-receptors that detect cold and cool temperatures and play pivotal roles in mediating the cold-induced vascular response. In this study, we investigated the role of TRPA1 and TRPM8 in the thermoregulatory behavioural respons...

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Main Authors: Dibesh Thapa, Brentton Barrett, Fulye Argunhan, Susan D. Brain
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/15/1/42
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author Dibesh Thapa
Brentton Barrett
Fulye Argunhan
Susan D. Brain
author_facet Dibesh Thapa
Brentton Barrett
Fulye Argunhan
Susan D. Brain
author_sort Dibesh Thapa
collection DOAJ
description The transient receptor potential (TRP) channels, TRPA1 and TRPM8, are thermo-receptors that detect cold and cool temperatures and play pivotal roles in mediating the cold-induced vascular response. In this study, we investigated the role of TRPA1 and TRPM8 in the thermoregulatory behavioural responses to environmental cold exposure by measuring core body temperature and locomotor activity using a telemetry device that was surgically implanted in mice. The core body temperature of mice that were cooled at 4 °C over 3 h was increased and this was accompanied by an increase in UCP-1 and TRPM8 level as detected by Western blot. We then established an effective route, by which the TRP antagonists could be administered orally with palatable food. This avoids the physical restraint of mice, which is crucial as that could influence the behavioural results. Using selective pharmacological antagonists A967079 and AMTB for TRPA1 and TRPM8 receptors, respectively, we show that TRPM8, but not TRPA1, plays a direct role in thermoregulation response to whole body cold exposure in the mouse. Additionally, we provide evidence of increased TRPM8 levels after cold exposure which could be a protective response to increase core body temperature to counter cold.
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spelling doaj.art-841b9a409cd04dfd9cb9667318ca026f2023-11-23T15:01:11ZengMDPI AGPharmaceuticals1424-82472021-12-011514210.3390/ph15010042Influence of Cold-TRP Receptors on Cold-Influenced BehaviourDibesh Thapa0Brentton Barrett1Fulye Argunhan2Susan D. Brain3Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, Franklin-Wilkins Building, Waterloo Campus, King’s College London, London SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, Franklin-Wilkins Building, Waterloo Campus, King’s College London, London SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, Franklin-Wilkins Building, Waterloo Campus, King’s College London, London SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, Franklin-Wilkins Building, Waterloo Campus, King’s College London, London SE1 9NH, UKThe transient receptor potential (TRP) channels, TRPA1 and TRPM8, are thermo-receptors that detect cold and cool temperatures and play pivotal roles in mediating the cold-induced vascular response. In this study, we investigated the role of TRPA1 and TRPM8 in the thermoregulatory behavioural responses to environmental cold exposure by measuring core body temperature and locomotor activity using a telemetry device that was surgically implanted in mice. The core body temperature of mice that were cooled at 4 °C over 3 h was increased and this was accompanied by an increase in UCP-1 and TRPM8 level as detected by Western blot. We then established an effective route, by which the TRP antagonists could be administered orally with palatable food. This avoids the physical restraint of mice, which is crucial as that could influence the behavioural results. Using selective pharmacological antagonists A967079 and AMTB for TRPA1 and TRPM8 receptors, respectively, we show that TRPM8, but not TRPA1, plays a direct role in thermoregulation response to whole body cold exposure in the mouse. Additionally, we provide evidence of increased TRPM8 levels after cold exposure which could be a protective response to increase core body temperature to counter cold.https://www.mdpi.com/1424-8247/15/1/42TRPA1TRPM8coldthermoregulationUCP-1BAT
spellingShingle Dibesh Thapa
Brentton Barrett
Fulye Argunhan
Susan D. Brain
Influence of Cold-TRP Receptors on Cold-Influenced Behaviour
Pharmaceuticals
TRPA1
TRPM8
cold
thermoregulation
UCP-1
BAT
title Influence of Cold-TRP Receptors on Cold-Influenced Behaviour
title_full Influence of Cold-TRP Receptors on Cold-Influenced Behaviour
title_fullStr Influence of Cold-TRP Receptors on Cold-Influenced Behaviour
title_full_unstemmed Influence of Cold-TRP Receptors on Cold-Influenced Behaviour
title_short Influence of Cold-TRP Receptors on Cold-Influenced Behaviour
title_sort influence of cold trp receptors on cold influenced behaviour
topic TRPA1
TRPM8
cold
thermoregulation
UCP-1
BAT
url https://www.mdpi.com/1424-8247/15/1/42
work_keys_str_mv AT dibeshthapa influenceofcoldtrpreceptorsoncoldinfluencedbehaviour
AT brenttonbarrett influenceofcoldtrpreceptorsoncoldinfluencedbehaviour
AT fulyeargunhan influenceofcoldtrpreceptorsoncoldinfluencedbehaviour
AT susandbrain influenceofcoldtrpreceptorsoncoldinfluencedbehaviour