Adenosine A2A receptors interact with GABAergic pathways to modulate respiration in neonatal piglets

Wilson, Christopher G.; Martin, Richard J.; Jaber, Marwan A.; Abu-Shaweesh, Jalal M.; Jafri, Anjun; Haxhiu, Musa A.; Zaidi, Syed I. A.

doi:10.1016/j.resp.2004.04.012

Cited by 64 publications

(56 citation statements)

References 36 publications

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“…Because blockade of either adenosinergic or GABAergic neurotransmission alone is sufficient to impair the acute HVR, it is likely that these two signalling molecules interact via the same cellular pathway in naked mole rats. This interaction is not surprising given that GABARs and adenosine receptors have been previously shown to interact in the control of breathing during development [31], presumably through adenosine-receptor mediated activation of GABAergic pathways since pre-treatment with GABAR antagonists prevents adenosine-mediated effects on ventilation in rats and piglets [32,33]. Taken together with our current results, marked similarities become apparent between respiratory controls in adult naked mole rats versus neonatal mammals.…”

Section: Discussionsupporting

confidence: 81%

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

et al. 2016

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ResearchCite this article: Chung D, Dzal YA, Seow A, Milsom WK, Pamenter ME. 2016 Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia. Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH). Conversely, naked mole rats do not hyperventilate in acute hypoxia and their response to CSH has not been examined. In this study, we explored mechanisms of plasticity in the control of the hypoxic ventilatory response (HVR) and hypoxic metabolic response (HMR) of freely behaving naked mole rats following 8-10 days of chronic sustained normoxia (CSN) or CSH. Specifically, we investigated the role of the major inhibitory neurotransmitter g-amino butyric acid (GABA) in mediating these responses. Our study yielded three important findings. First, naked mole rats did not exhibit ventilatory plasticity following CSH, which is unique among adult animals studied to date. Second, GABA receptor (GABAR) antagonism altered breathing patterns in CSN and CSH animals and modulated the acute HVR in CSN animals. Third, naked mole rats exhibited GABAR-dependent metabolic plasticity following longterm hypoxia, such that the basal metabolic rate was approximately 25% higher in normoxic CSH animals than CSN animals, and GABAR antagonists modulated this increase.

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Section: Discussionsupporting

confidence: 81%

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

et al. 2016

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“…2) Mutant pups developed intermittent periods of apnea up to two times per hour and up to 20 seconds in duration, which contributed to lethal outcome during the first days after birth (Boison et al, 2002b). Periods of apnea in the mutant pups is consistent with increased activation of adenosine receptors in brain stem, which contribute to the control of respiratory function (Aoki et al, 2004;Wilson et al, 2004). 3) From postnatal day 4 onward, Adk 2/2 mutants developed microvesicular hepatic steatosis and failed to thrive as evidenced by significantly reduced weight gain and early death: 35% of the mutants died within the first 4 days of life, 53% between postnatal day 5 and 8, and only 12% survived up to 14 days.…”

Section: A Lessons From Genetically Modified Organismsmentioning

confidence: 99%

Adenosine Kinase: Exploitation for Therapeutic Gain

2013

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“…A 2A receptors interact with GABAergic pathways in the medulla oblongata to modulate respiration in neonatal piglets (Wilson et al, 2004), whereas A 1 receptors were reported to modulate the activities of both inspiratory and expiratory neurons in the medial region of the nucleus retrofacialis of neonatal rats (Wang et al, 2005). Activation of central A 2A receptors enhances superior laryngeal nerve stimulation-induced apnea in piglets via a GABAergic pathway (Abu-Shaweesh, 2007).…”

Section: Central Control Of Respirationmentioning

confidence: 99%