Effect of the sympathetic nervous system co-transmitters ATP and norepinephrine on thermoregulatory response to cooling
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Updated: Mar 20, 2026

Measuring Skeletal Muscle Thermogenesis in Mice and Rats
Published on: July 27, 2022
Tamara V Kozyreva1, Ekaterina S Meyta2, Galina M Khramova2
1Department of Thermophysiology; Institute of Physiology and Fundamental Medicine; Russian Academy of Sciences; Novosibirsk, Russia; Novosibirsk State University; Novosibirsk, Russia.
Abstract:
The existence of co-transmitters of the sympathetic nervous system norepinephrine (NE) and ATP implies variations in the neuromodulator mechanisms of physiological processes. The role of ATP, as a transmitter of the peripheral part of sympathetic nervous system in the formation of thermoregulatory response is not clear. Whether ATP modulates any parameters of thermoregulatory response to cold; if yes, whether co-transmitters of sympathetic nervous system ATP and NE differently modulate thermoregulatory response and on which parameters of cold-defense response the influence of ATP is more pronounced. Experiments were carried out on rats. ATP (10(-6)), NE (10(-3)), and their mixture introduced iontophoretically into skin. Their effects on thermoregulatory parameters (temperature parameters, total oxygen consumption, carbon dioxide release, muscle activity, respiratory coefficient) were studied in thermoneutral conditions (without cold load) and under the cooling. In thermoneutral conditions both ATP and NE enhance total metabolism through increase in metabolic rate of lipids, NE effect being more expressed. It was shown that ATP and NE influence predominantly on the different components of the metabolic response to cold. ATP affects to the greatest extent on cold muscular thermogenesis by increasing shivering almost twofold and lowering its initiation temperature thresholds, whereas NE mainly promotes increase in non-shivering thermogenesis. When introducing the mixture of these biological substances the effect of NE is more expressed and the ATP effect is weakened. The obtained results allow to suggest that in vivo the NE effects can be more expressed when the sympathetic nervous system is stimulated by cold. Thus, NE and ATP being co-transmitters and predominantly acting on the different processes of cold thermogenesis (ATP on shivering and NE on non-shivering) may organize the certain sequence of cold defense responses.
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