New research in The FASEB Journal suggests that blocking TRPV1 protein causes an increased release of noradrenaline, leading to an increase in core body temperatures.
New research published online in The FASEB Journal suggests that the fight or flight response that we experience in stressful situations may be controlled by a protein called TRPV1. In the mouse study, researchers found that TRPV1 controls the nerves that release noradrenaline and affect core body temperature. This opens the doors for the development of new strategies to treat the effects of stress on the body.
“The findings of our study give a greater insight into how body temperature is controlled, vital to improving the control of core body temperature in situations such as anesthesia, drug overdose and diseases in which core body temperature is pathologically abnormal,” said Julie Keeble, Ph.D., a researcher involved in the work from the Institute of Pharmaceutical Science at King’s College in London, England.
To make this discovery, Keeble and colleagues conducted experiments using normal mice and mice bred to have no TRPV1 protein in their bodies. Drugs that blocked TRPV1 were administered to normal mice and their body temperature increased. The same drugs had no effect in the genetically altered mice. Normal mice that were given drugs that blocked the effects of noradrenaline before giving the TRPV1 blocker demonstrated a much smaller increase in body temperature. The genetically altered mice surprisingly showed a normal body temperature under normal conditions, which led to further study. The researchers found that the “fight or flight” response in the mice was reduced, including after administration of amphetamine, which is known to increase levels of noradrenaline.
“This protein, TRPV1, present on our nerve cells, has been known to control pain. Now we learn that it is also critical for controlling body temperature in response to stress hormones like adrenaline,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “It sheds a new molecular light on the ‘switch’ that controls a good part of the body’s preparation for “fight or flight” response, first described by Harvard’s Walter B. Cannon almost a century ago.”
About this neuroscience research
Source: Cody Mooneyhan – FASEB Image Credit: The image is in the public domain Original Research:Abstract research for “The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature” by Khadija M. Alawi, Aisah A. Aubdool, Lihuan Liang, Elena Wilde, Abhinav Vepa, Maria-Paraskevi Psefteli, Susan D. Brain, and Julie E. Keeble in The FASEB Journal. Published online July 1 2015 doi:10.1096/fj.15-272526
The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature
Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. D-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature.
“The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature” by Khadija M. Alawi, Aisah A. Aubdool, Lihuan Liang, Elena Wilde, Abhinav Vepa, Maria-Paraskevi Psefteli, Susan D. Brain, and Julie E. Keeble in The FASEB Journal. Published online July 1 2015 doi:10.1096/fj.15-272526