Abstract
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.
Highlights
Pharmaceuticals 2022, 15, 42. https://Mammals possess several mechanisms to adapt to temperature changes to preserve physiological homeostasis and conserve core body temperature [1]
The specific objectives of this study were to; (i) investigate the core body temperature changes in response to environmental cold exposure in comparison to room temperature; (ii) examine the protein expression of uncoupling protein 1 (UCP-1), a key modulator of thermogenesis, and TRPM8 in mice that were exposed to environmental cold; and (iii) use pharmacological antagonists of TRPA1 and TRPM8 to decipher the activity of these transient receptor potential (TRP) channels in thermogenesis
room temperature (RT) treatment (n = 6). (I) the initial temperature increase at the start of cold exposure in the interestingly our results showed that the cold exposure caused an increase climatic chamber or RT treatment; (J) the minimum temperature that was achieved during 3 h of in brown adipose tissue (BAT) TRPM8 protein expression, as determined by Western blot (Figure 2B), suggesting
Summary
Mammals possess several mechanisms to adapt to temperature changes to preserve physiological homeostasis and conserve core body temperature [1]. One example of such a mechanism that is involved in maintaining core body temperature when exposed to the cold is the cutaneous vasoconstriction response that is often clearly observed in the extremities of the body such as the fingers and toes [1,2]. The body induces further protective mechanisms against the cold to maintain core body temperature; shivering and non-shivering thermogenesis. Within the past 20 years, the understanding of cold sensation via cell sensors and receptors has advanced, but it has only been within the last decade that studies have been conducted to link the cold sensors with thermogenesis.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call