NMDA Receptors of A5 Area in the Regulation of Blood Pressure and Respiratory Activity during Hypoxia in Rats

Pyatin, V. F.; Tatarnikov, V. S.

doi:10.1007/s10517-015-2980-z

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…Pyatin et al . 44 have suggested that NMDARs in A5 neurons, mediate blood pressure shifts during hypoxia. They show that the blood pressure drop in mice from induced hypoxia is significantly accentuated when NMDARs in A5 neurons are blocked as compared with mice whose receptors are not blocked.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms involved in the side effects of fatty acid amide hydrolase inhibitors: a structural phenomics approach to proteome-wide cellular off-target deconvolution and disease association

Dider

Zhao

et al. 2016

npj Syst Biol Appl

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Fatty acid amide hydrolase (FAAH) is a promising therapeutic target for the treatment of pain and CNS disorders. However, the development of potent and safe FAAH inhibitors is hindered by their off-target mediated side effect that leads to brain cell death. Its physiological off-targets and their associations with phenotypes may not be characterized using existing experimental and computational techniques as these methods fail to have sufficient proteome coverage and/or ignore native biological assemblies (BAs; i.e., protein quaternary structures). To understand the mechanisms of the side effects from FAAH inhibitors and other drugs, we develop a novel structural phenomics approach to identifying the physiological off-targets binding profile in the cellular context and on a structural proteome scale, and investigate the roles of these off-targets in impacting human physiology and pathology using text mining-based phenomics analysis. Using this integrative approach, we discover that FAAH inhibitors may bind to the dimerization interface of NMDA receptor (NMDAR) and several other BAs, and thus disrupt their cellular functions. Specifically, the malfunction of the NMDAR is associated with a wide spectrum of brain disorders that are directly related to the observed side effects of FAAH inhibitors. This finding is consistent with the existing literature, and provides testable hypotheses for investigating the molecular origin of the side effects of FAAH inhibitors. Thus, the in silico method proposed here, which can for the first time predict proteome-wide drug interactions with cellular BAs and link BA–ligand interaction with clinical outcomes, can be valuable in off-target screening. The development and application of such methods will accelerate the development of more safe and effective therapeutics.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms involved in the side effects of fatty acid amide hydrolase inhibitors: a structural phenomics approach to proteome-wide cellular off-target deconvolution and disease association

Dider

Zhao

et al. 2016

npj Syst Biol Appl

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Integration of the Proprioceptive and Central Inspiratory Inhibitory Afferent Inputs by Pontine Noradrenergic A5 Neurons in Rats

et al. 2018

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Inhibitory afferent inputs to pontine A5 noradrenergic neurons (A5 NN) are not known, except partial baroreceptor input. In spontaneously breathing pentobarbital-anesthetized rats, we registered 35 A5 NN that were activated by hypoxia (100% N, 10 sec) by more than 5 times in comparison with the background. Cooling of retrotrapezoid nucleus (15°C, 6 sec) completely blocked the motor inspiratory output and A5 NN discharge frequency increased (23/23) by more than 7 times in comparison with the background values. The beginning of A5 NN activation coincided with cessation of inspiratory activity. Short-term passive stretching of the shin muscles (1 sec, 100 g) caused BP drop and complete inhibition of A5 NN (12/12) activated by hypoxia. Inhibitory afferent inputs from proprioceptors and central inspiratory neurons that can limit A5 NN activity were demonstrated.

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Circular RNAs in rat models of cardiovascular and renal diseases

Cheng

Joe

2017

Physiological Genomics

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Circular RNAs (circRNAs) have emerged as an important new class of genomic regulatory molecules contributing to the development of various diseases, but their relevance to the development and progression of hypertension remains largely unknown. A major impediment to begin studying circRNAs in rat models of inherited hypertension is that the rat as a valuable model of human diseases lags far behind the mouse and human in providing knowledge on circRNAs. In this study, a genome-wide circRNA profiling was performed from four rat strains that are widely used in hypertension research: the Dahl salt-sensitive rat (S), the Dahl salt-resistant rat (R), the spontaneously hypertensive rat (SHR), and the Wistar Kyoto rat (WKY). Combined hybridization data obtained from these four strains allowed for the identification of 12,846 circRNAs as being expressed in the rat kidneys. Out of these, 318 and 110 circRNAs were differentially expressed with a fold change > 1.5 ( < 0.05) in S vs. R and SHR vs. WKY, respectively. Among these circRNAs, circRNA/microRNA interaction was predicted since circRNAs are known as microRNA sponges to sequester microRNAs. Several circRNAs were further validated by quantitative real-time PCR. To our knowledge, our study is the primary report of profiling circRNAs in renal tissue and illustrates that circRNAs could be candidate genetic factors controlling blood pressure.

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NMDA Receptors of A5 Area in the Regulation of Blood Pressure and Respiratory Activity during Hypoxia in Rats

Cited by 3 publications

References 12 publications

Molecular mechanisms involved in the side effects of fatty acid amide hydrolase inhibitors: a structural phenomics approach to proteome-wide cellular off-target deconvolution and disease association

Molecular mechanisms involved in the side effects of fatty acid amide hydrolase inhibitors: a structural phenomics approach to proteome-wide cellular off-target deconvolution and disease association

Integration of the Proprioceptive and Central Inspiratory Inhibitory Afferent Inputs by Pontine Noradrenergic A5 Neurons in Rats

Circular RNAs in rat models of cardiovascular and renal diseases

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