P2X3 receptor antagonism reduces the occurrence of apnoeas in newborn rats

Katayama, Pedro L.; Abdala, Ana Paula; Charles, Ian; Pijacka, Wioletta; Salgado, Hélio César; Gever, Joel R.; Ford, Anthony; Paton, Julian F. R.

doi:10.1016/j.resp.2020.103438

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…A large variety of metabolites, including leptin, insulin and glucose, can also modulate CB activity (Kim & Polotsky, 2020; Ortega‐Sáenz & López‐Barneo, 2020). The blockade of purinergic receptors P2 × 2/3 and the modulation of gasotransmitters in the CB have showed promising benefits in the treatment of SDB (Katayama et al., 2020; Kim & Polotsky, 2020; Peng et al., 2010). However, their association with TRPM7 signalling in the CB has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…In response to hypoxaemia and hypercapnia, CB are activated to induce hyperventilation (Eldridge, 1974; Gonzalez‐Martín et al., 2011; Lindsey et al., 2018; Nurse & Piskuric, 2013; Ortega‐Sáenz & López‐Barneo, 2020; Silva & Schreihofer, 2011). Pharmacological attenuation of CB activity may reduce apnoeas in mice (Katayama et al., 2020; Kim & Polotsky, 2020). Obesity is associated with augmented hypoxic chemoreflex during sleep, which can exacerbate hypoventilation and SDB (Narkiewicz, Kato et al., 1999; Narkiewicz, van de Borne et al., 1999; Van De Borne et al., 2001).…”

Section: Introductionmentioning

confidence: 99%

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TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies

Kim

Shin

Pho

et al. 2022

The Journal of Physiology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies

Kim

Shin

Pho

et al. 2022

The Journal of Physiology

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“…Because of its multisensory ability and integrative role, it is somewhat expected that a CB dysfunction could impact the activity of different organs/systems and, thus, contribute to various diseases. Numerous pre-clinical and clinical studies have shown that CB dysfunction, usually characterized by its overactivity, plays a role in hypertension ( 83 – 85 ), heart failure ( 86 , 87 ), apneas of prematurity ( 88 , 89 ), and metabolic diseases ( 90 , 91 ). In hypertension and heart failure, for example, a chronic CB overactivation has been associated with the sustained activation of the sympathetic nervous system, which contributes to the development and maintenance of these conditions ( 83 , 87 , 92 – 95 ).…”

Section: Targeting the Cb As A Therapeutic Approach For Inflammatory ...mentioning

confidence: 99%

The carotid body: A novel key player in neuroimmune interactions

et al. 2022

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United States; The idea that the nervous system communicates with the immune system to regulate physiological and pathological processes is not new. However, there is still much to learn about how these interactions occur under different conditions. The carotid body (CB) is a sensory organ located in the neck, classically known as the primary sensor of the oxygen (O2) levels in the organism of mammals. When the partial pressure of O2 in the arterial blood falls, the CB alerts the brain which coordinates cardiorespiratory responses to ensure adequate O2 supply to all tissues and organs in the body. A growing body of evidence, however, has demonstrated that the CB is much more than an O2 sensor. Actually, the CB is a multimodal sensor with the extraordinary ability to detect a wide diversity of circulating molecules in the arterial blood, including inflammatory mediators. In this review, we introduce the literature supporting the role of the CB as a critical component of neuroimmune interactions. Based on ours and other studies, we propose a novel neuroimmune pathway in which the CB acts as a sensor of circulating inflammatory mediators and, in conditions of systemic inflammation, recruits a sympathetic-mediated counteracting mechanism that appears to be a protective response.

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“…Dr. Julian Paton’s laboratory has shown that purinergic signaling may play a crucial role in the generation of aberrant chemoreflex responses in the CB, leading to hypertension and sleep-disordered breathing. Hence, the pharmacological antagonism of purinergic receptors in the CB has been proposed as a potential pharmacological approach to normalizing blood pressure and breathing stability [ 212 , 213 ] ( Table 1 ). Leptin-mediated TRPM7 channels: Our group has shown that leptin acts in the CB and increases CSN activity to increase blood pressure through the activation of TRPM7 channels [ 96 , 97 ].…”

Section: Cb Manipulations: Therapeutic Targets For Metabolic Syndrmentioning

confidence: 99%

“…Antagonism of P2X2/3 receptors AF-219 and AF-454 1-AF-219 and AF-454 are highly selective P2X3 receptor antagonists and AF-219 was clinically tested to treat patients with refractory chronic cough [215]; 2-In SH rats, AF-219 administered to the CB reduced the blood pressure in a dose-dependent manner and decreased the sympathetic tone [212]; 3-Systemic administration of AF-454 blunted the HVR and reduced the occurrence of apneas in newborn rats [213].…”

Section: Purinergic Systemmentioning

confidence: 99%

Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets

Kim

Polotsky

2020

IJMS

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The carotid body (CB) is responsible for the peripheral chemoreflex by sensing blood gases and pH. The CB also appears to act as a peripheral sensor of metabolites and hormones, regulating the metabolism. CB malfunction induces aberrant chemosensory responses that culminate in the tonic overactivation of the sympathetic nervous system. The sympatho-excitation evoked by CB may contribute to the pathogenesis of metabolic syndrome, inducing systemic hypertension, insulin resistance and sleep-disordered breathing. Several molecular pathways are involved in the modulation of CB activity, and their pharmacological manipulation may lead to overall benefits for cardiometabolic diseases. In this review, we will discuss the role of the CB in the regulation of metabolism and in the pathogenesis of the metabolic dysfunction induced by CB overactivity. We will also explore the potential pharmacological targets in the CB for the treatment of metabolic syndrome.

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P2X3 receptor antagonism reduces the occurrence of apnoeas in newborn rats

Cited by 5 publications

References 35 publications

TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies

TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies

The carotid body: A novel key player in neuroimmune interactions

Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets

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