Orexin-A Excites Airway Vagal Preganglionic Neurons via Activation of Orexin Receptor Type 1 and Type 2 in Rats

Abstract

Airway vagal nerves play a predominant role in the neural control of the airway, and augmented airway vagal activity is known to play important roles in the pathogenesis of some chronic inflammatory airway diseases. Several lines of evidence indicate that dysfunctional central orexinergic system is closely related to the severity of airway diseases, however, whether orexins affect airway vagal activity is unknown. This study investigates whether and how orexin-A regulates the activity of medullary airway vagal preganglionic neurons (AVPNs). The expression of orexin receptor type 1 (OX1R) and type 2 (OX2R) was examined using immunofluorescent staining. The effects of orexin-A on functionally identified inspiratory-activated AVPNs (IA-AVPNs), which are critical in the control of airway smooth muscle, were examined using patch-clamp in medullary slices of neonatal rats. Airway vagal response to injection of orexin-A into the magna cisterna was examined using plethysmography in juvenile rats. The results show that retrogradely labeled AVPNs were immunoreactive to anti-OX1R antibody and anti-OX2R antibody. Orexin-A dose-dependently depolarized IA-AVPNs and increased their firing rate. In synaptically isolated IA-AVPNs, the depolarization induced by orexin-A was blocked partially by OX1R antagonist SB-334867 or OX2R antagonist TCS OX2 29 alone, and completely by co-application of both antagonists. The orexin-A-induced depolarization was also mostly blocked by Na+/Ca2+ exchanger inhibitor KB-R7943. Orexin-A facilitated the glutamatergic, glycinergic and GABAergic inputs to IA-AVPNs, and the facilitation of each type of input was blocked partially by SB-334867 or TCS OX2 29 alone, and completely by co-application of both antagonists. Injection of orexin-A into the magna cisterna of juvenile rats significantly increased the inspiratory and expiratory resistance of the airway and consequently decreased the dynamic compliance of the lungs, all of which were prevented by atropine sulfate or bilateral vagotomy. These results demonstrate that orexin-A excites IA-AVPNs via activation of both OX1R and OX2R, and suggest that increased central synthesis/release of orexins might participate in the pathogenesis of airway diseases via over-activation of AVPNs.

Transtorno de estresse pós-traumático e interações psicofisiológicas de padrões cerebrais, exercício e tratamento não medicamentoso: uma revisão integrativa

“…Orexin plays an important role in the activation of the activity of the sympathetic nervous system and in the stress responses of the HPA axis, so that the activation of orexin prevents the extinction of fear and promotes avoidance behaviors, factors also observed by Porges (26)(27)(28) symptoms and vagus nerve dysregulation. Studies investigating changes in brain physiology resulting from laboratory interventions are carried out in animal models; regarding the relationship between orexin and the vagus nerve, studies of this type have indicated that the expression of orexin coincides with the cerebral innervation of the vagus nerve, influencing respiratory activity (39) and that its presence in the prefrontal cortex may be involved in the wakefulness-promoting effects of vagus nerve stimulation (40).…”

Arousal from sleep, alertness induced by bimodal signals during “environment-person” communication

“…The focal specific sensitivity to changes in CO 2 and H + concentrations is also important for a sensitive response to hypoxic signals (lack of oxygen supply) from the external and internal environment [1,2]. It is also important that the orexinergic activating system does not act alone, but as an integral part of a single complex system of regulatory chemosensitive centers: RTN (retrotrapezoid nucleus); the raphe nucleus, the caudal NTS (nucleus of the solitary tract), the locus coeruleus (LC), the caudal ventral medulla, the pre-Bötzinger complex (the pre-Bötzinger complex in the ventral respiratory center of the brainstem medulla), and the perifornical region of the lateral hypothalamus [3][4][5][6][7][8][9]. Along with the suprachiasmatic nucleus of the hypothalamus, the orexinergic activating center is modulated by signals of various physical modalities about the circadian cycle from the external environment.…”