Effect of the sympathetic nervous system co-transmitters ATP and norepinephrine on thermoregulatory response to cooling

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.

Precise Control of Target Temperature Using N6-Cyclohexyladenosine and Real-Time Control of Surface Temperature

“…Studies show that the rate of oxygen consumption decreases before the drop in T b during onset of hibernation and that HR is a proxy for metabolic rate (Currie et al, 2014). Rapid onset of bradycardia in the current study is consistent with metabolic suppression secondary to the inhibition of thermogenesis (Kozyreva et al, 2015).…”

Neuronal control of experimental colitis occurs via sympathetic intestinal innervation

“…Considering this, we do not anticipate that the ambient temperature during experimentation affects sympathetic activation to interfere with our observations. Furthermore, research into cold stress and the effect of low temperatures on the sympathetic nervous system usually study temperatures around 4 °C . Lastly, the sympathetic activation upon cold stress does not act at the same level on different tissues like brown adipose tissue and the intestine …”

“…Furthermore, research into cold stress and the effect of low temperatures on the sympathetic nervous system usually study temperatures around 4 °C. [41][42][43] Lastly, the sympathetic activation upon cold stress does not act at the same level on different tissues like brown adipose tissue and the intestine. 44 F I G U R E 6 Stimulation of the superior mesenteric nerve did not change other indicators of DSS-induced colitis.…”

General Principles of Neuronal Co-transmission: Insights From Multiple Model Systems

“…ATP has been subsequently found to co-localize with various transmitters in the peripheral and CNS (see Table 1 and reviews by Westfall et al, 1978; Burnstock, 2007; Wier et al, 2009; Hill-Eubanks et al, 2010; Hnasko and Edwards, 2012; Kennedy, 2015). For example, purinergic co-transmission is involved in the sympathetic control of arterial pressure in rats (Emonnot et al, 2006); as a co-transmitter with ACh in carotid body arterial chemoreceptors (Zapata, 2007); in the human carotid body where ACh, ATP and cytokines are co-released during hypoxia (Kåhlin et al, 2014); ATP and glutamate are released ectopically from vesicles along axons to mediate neurovascular coupling via glial calcium signaling (Thyssen et al, 2010); co-localized ATP and NA are involved in the sympathetic thermoregulatory response to cooling (Kozyreva et al, 2015); and ATP is released from dopaminergic neurons of the mouse retina and midbrain (Ho et al, 2015). For reviews describing the physiological significance of purinergic co-transmission see Burnstock (2004, 2014).…”