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Nanduri R. Prabhakar - One of the best experts on this subject based on the ideXlab platform.
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Oxygen Sensing by the Carotid Body: Past and Present
Advances in Experimental Medicine and Biology, 2017Co-Authors: Nanduri R. Prabhakar, Yingjie PengAbstract:It is now well established that Carotid bodies are sensory organs for monitoring arterial blood oxygen levels and trigger reflexes that are critical for maintaining homeostasis during hypoxemia. This review article provides a brief account of the early studies leading to the discovery of the Carotid Body as a sensory receptor and addresses current views of O2 sensing mechanism(s) in the Carotid Body and their physiological importance.
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regulation of Carotid Body oxygen sensing by hypoxia inducible factors
Pflügers Archiv: European Journal of Physiology, 2016Co-Authors: Nanduri R. Prabhakar, Gregg L SemenzaAbstract:Oxygen (O2) sensing by the Carotid Body and its chemosensory reflex is critical for homeostatic regulation of breathing and blood pressure. Carotid Body responses to hypoxia are not uniform but instead exhibit remarkable inter-individual variations. The molecular mechanisms underlying variations in Carotid Body O2 sensing are not known. Hypoxia-inducible factor-1 (HIF-1) and HIF-2 mediate transcriptional responses to hypoxia. This article reviews the emerging evidence that proper expression of the HIF-α isoforms is a key molecular determinant for Carotid Body O2 sensing. HIF-1α deficiency leads to a blunted Carotid Body hypoxic response, which is due to increased abundance of HIF-2α, elevated anti-oxidant enzyme activity, and a reduced intracellular redox state. Conversely, HIF-2α deficiency results in augmented Carotid Body sensitivity to hypoxia, which is due to increased abundance of HIF-1α, elevated pro-oxidant enzyme activity, and an oxidized intracellular redox state. Double heterozygous mice with equally reduced HIF-1α and HIF-2α showed no abnormality in redox state or Carotid Body O2 sensing. Thus, mutual antagonism between HIF-α isoforms determines the redox state and thereby establishes the set point for hypoxic sensing by the Carotid Body.
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Carbon monoxide (CO) and hydrogen sulfide (H2S) in hypoxic sensing by the Carotid Body
Respiratory Physiology and Neurobiology, 2012Co-Authors: Nanduri R. PrabhakarAbstract:Carotid bodies are sensory organs for monitoring arterial blood oxygen (O2) levels, and the ensuing reflexes maintain cardio-respiratory homeostasis during hypoxia. This article provides a brief update of the role of carbon monoxide (CO) and hydrogen sulfide (H2S) in hypoxic sensing by the Carotid Body. Glomus cells, the primary site of O2sensing in the Carotid Body express heme oxygenase-2 (HO-2), a CO catalyzing enzyme. HO-2 is a heme containing enzyme and has high affinity for O2. Hypoxia inhibits HO-2 activity and reduces CO generation. Pharmacological and genetic approaches suggest that CO inhibits Carotid Body sensory activity. Stimulation of Carotid Body activity by hypoxia may reflect reduced formation of CO. Glomus cells also express cystathionine γ-lyase (CSE), an H2S generating enzyme. Exogenous application of H2S donors, like hypoxia, stimulate the Carotid Body activity and CSE knockout mice exhibit severely impaired sensory excitation by hypoxia, suggesting that CSE catalyzed H2S is an excitatory gas messenger. Hypoxia increases H2S generation in the Carotid Body, and this response was attenuated or absent in CSE knockout mice. HO inhibitor increased and CO donor inhibited H2S generation. It is proposed that Carotid Body response to hypoxia requires interactions between HO-2-CO and CSE-H2S systems. © 2012 Elsevier B.V.
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Hydrogen sulfide (H2S): A physiologic mediator of Carotid Body response to hypoxia
Advances in Experimental Medicine and Biology, 2012Co-Authors: Nanduri R. PrabhakarAbstract:Carotid bodies are sensory organs for monitoring arterial blood O 2 levels. Nitric oxide and carbon monoxide function as inhibitory gasotransmitters in the Carotid Body. Hydrogen sulfide (H2S) is another emerging gasotransmitter. The purpose of this article is to review recent studies addressing the role of H2S in Carotid Body.Cystathionine γ-lyase (CSE) and cystathionine β synthase (CBS) are the two major enzymes that catalyze the formation of endogenous H2S. Both CSE and CBS are expressed in glomus cells, the putative site of sensorytransduction in the Carotid Body. Hypoxia increases H2S generation in the Carotid Body. CSE knockout mice displayed absence of hypoxia-evoked H2S generation and severely impaired sensory excitation by low O2. Pharmacological inhibitors of CSE as well as CBS showed a similar phenotype in mice and rats. Like hypoxia, H2S donors stimulated the Carotid Body sensory activity and this response required Ca2+ influx via voltage-gated Ca2+ channels. Evidence is emerging implicating Ca2+ activated K+ channels in glomus cells as potential targets of H2S. © Springer Science+Business Media Dordrecht 2012.
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peripheral chemoreceptors function and plasticity of the Carotid Body
Comprehensive Physiology, 2012Co-Authors: Prem Kumar, Nanduri R. PrabhakarAbstract:The discovery of the sensory nature of the Carotid Body dates back to the beginning of the 20th century. Following these seminal discoveries, research into Carotid Body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the Carotid Body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the Carotid Body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the Carotid Body and its implications. It is clear that the sensory function of the Carotid Body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of Carotid Body plasticity in health and disease are discussed in the final sections of this article.
S Snyder - One of the best experts on this subject based on the ideXlab platform.
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h2s mediates o2 sensing in the Carotid Body
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Yingjie Peng, Jayasri Nanduri, Gayatri Raghuraman, Dangjai Souvannakitti, Moataz M Gadalla, Ganesh K Kumar, S Snyder, Nanduri R. PrabhakarAbstract:Gaseous messengers, nitric oxide and carbon monoxide, have been implicated in O2 sensing by the Carotid Body, a sensory organ that monitors arterial blood O2 levels and stimulates breathing in response to hypoxia. We now show that hydrogen sulfide (H2S) is a physiologic gasotransmitter of the Carotid Body, enhancing its sensory response to hypoxia. Glomus cells, the site of O2 sensing in the Carotid Body, express cystathionine γ-lyase (CSE), an H2S-generating enzyme, with hypoxia increasing H2S generation in a stimulus-dependent manner. Mice with genetic deletion of CSE display severely impaired Carotid Body response and ventilatory stimulation to hypoxia, as well as a loss of hypoxia-evoked H2S generation. Pharmacologic inhibition of CSE elicits a similar phenotype in mice and rats. Hypoxia-evoked H2S generation in the Carotid Body seems to require interaction of CSE with hemeoxygenase-2, which generates carbon monoxide. CSE is also expressed in neonatal adrenal medullary chromaffin cells of rats and mice whose hypoxia-evoked catecholamine secretion is greatly attenuated by CSE inhibitors and in CSE knockout mice.
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carbon monoxide a role in Carotid Body chemoreception
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Nanduri R. Prabhakar, Jay L Dinerman, Faton Agani, S SnyderAbstract:Abstract Carbon monoxide (CO), produced endogenously by heme oxygenase, has been implicated as a neuronal messenger. Carotid bodies are sensory organs that regulate ventilation by responding to alterations of blood oxygen, CO2, and pH. Changes in blood gases are sensed by glomus cells in the Carotid Body that synapse on afferent terminals of the Carotid sinus nerve that projects to respiratory-related neurons in the brainstem. Using immunocytochemistry, we demonstrate that heme oxygenase 2 is localized to glomus cells in the cat and rat Carotid bodies. Physiological studies show that zinc protoporphyrin IX, a potent heme oxygenase inhibitor, markedly increases Carotid Body sensory activity, while copper protoporphyrin IX, which does not inhibit the enzyme, is inactive. Exogenous CO reverses the stimulatory effects of zinc protoporphyrin IX. These results suggest that glomus cells are capable of synthesizing CO and endogenous CO appears to be a physiologic regulator of Carotid Body sensory activity.
Alice B Smith - One of the best experts on this subject based on the ideXlab platform.
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paraganglioma Carotid Body tumor
Head and Neck Pathology, 2009Co-Authors: Jacqueline A Wieneke, Alice B SmithAbstract:Extra-adrenal paragangliomas are neoplasms of the paraganglia located within the paravertebral sympathetic and parasympathetic chains. Thus paragangliomas may arise anywhere along these tracts and common sites of occurrence include abdomen, retroperitoneum, chest and mediastinum and various head and neck locations such as jugulotympanic membrane, orbit, nasopharynx, larynx, vagal Body and Carotid Body. Recent literature suggests a molecular basis for the development of some paragangliomas, i.e. germline mutations. Six genes have been identified and are thought to contribute to the development of pheochromocytoma/paraganglioma. These include RET, VHL, NF1 and SDH subunits SDHB, SDHC, and SDHD. SDHD and SDHB mutations account for a significant percentage of head and neck paragangliomas. It is well know that paragangliomas may be hereditary and may be part of genetic syndromes such as Von Hippel-Lindau syndrome, neurofibromatosis type I (von Recklinghausen disease), MEN 2A and MEN 2B. When features of these more commonly known syndromes are not present, many familial cases, often associated with the above mentioned germline mutations, go unrecognized. In the head and neck region the normal paraganglia are associated with the parasympathetic nervous system and paragangliomas arising from these parasympathetic sites account for up to 70% of extra-adrenal paragangliomas. The most common site is the Carotid Body. Carotid Body paragangliomas arise at the bifurcation of the internal and external Carotid arteries and have classic radiographic
Yingjie Peng - One of the best experts on this subject based on the ideXlab platform.
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Oxygen Sensing by the Carotid Body: Past and Present
Advances in Experimental Medicine and Biology, 2017Co-Authors: Nanduri R. Prabhakar, Yingjie PengAbstract:It is now well established that Carotid bodies are sensory organs for monitoring arterial blood oxygen levels and trigger reflexes that are critical for maintaining homeostasis during hypoxemia. This review article provides a brief account of the early studies leading to the discovery of the Carotid Body as a sensory receptor and addresses current views of O2 sensing mechanism(s) in the Carotid Body and their physiological importance.
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h2s mediates o2 sensing in the Carotid Body
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Yingjie Peng, Jayasri Nanduri, Gayatri Raghuraman, Dangjai Souvannakitti, Moataz M Gadalla, Ganesh K Kumar, S Snyder, Nanduri R. PrabhakarAbstract:Gaseous messengers, nitric oxide and carbon monoxide, have been implicated in O2 sensing by the Carotid Body, a sensory organ that monitors arterial blood O2 levels and stimulates breathing in response to hypoxia. We now show that hydrogen sulfide (H2S) is a physiologic gasotransmitter of the Carotid Body, enhancing its sensory response to hypoxia. Glomus cells, the site of O2 sensing in the Carotid Body, express cystathionine γ-lyase (CSE), an H2S-generating enzyme, with hypoxia increasing H2S generation in a stimulus-dependent manner. Mice with genetic deletion of CSE display severely impaired Carotid Body response and ventilatory stimulation to hypoxia, as well as a loss of hypoxia-evoked H2S generation. Pharmacologic inhibition of CSE elicits a similar phenotype in mice and rats. Hypoxia-evoked H2S generation in the Carotid Body seems to require interaction of CSE with hemeoxygenase-2, which generates carbon monoxide. CSE is also expressed in neonatal adrenal medullary chromaffin cells of rats and mice whose hypoxia-evoked catecholamine secretion is greatly attenuated by CSE inhibitors and in CSE knockout mice.
Thomas C Calcaterra - One of the best experts on this subject based on the ideXlab platform.
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surgical management of Carotid Body tumors
Otolaryngology-Head and Neck Surgery, 1999Co-Authors: Steven J Wang, Marilene B Wang, Tanya M Barauskas, Thomas C CalcaterraAbstract:Abstract Objective: The goal was to review our experience in the management of Carotid Body tumors at a tertiary referral center. Methods: A retrospective review was performed of patients at University of California-Los Angeles Medical Center in whom Carotid Body tumor was diagnosed between 1973 and 1998. Results: Twenty-nine patients with 36 Carotid Body tumors were identified. Thirty-five operations were performed. Seventeen patients underwent preoperative embolization. The blood loss for these patients was less than for those without embolization. Five patients had preoperative cranial nerve deficits. Neurologic deficits were noted in 41% of patients immediately after surgery. In 24% of patients, the deficits were permanent. Conclusion: Surgical resection is the treatment of choice for Carotid Body tumors. Embolization immediately before surgery decreases blood loss and facilitates tumor removal. In our series, the risk of new postsurgical cranial nerve deficits was small. Observation of these tumors is not recommended because progressive growth is associated with increased risk of neurologic deficits. (Otolaryngol Head Neck Surg 2000;123:202–6.)