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      Fernando de Castro and the discovery of the arterial chemoreceptors

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          Abstract

          When de Castro entered the carotid body (CB) field, the organ was considered to be a small autonomic ganglion, a gland, a glomus or glomerulus, or a paraganglion. In his 1928 paper, de Castro concluded: “In sum, the Glomus caroticum is innervated by centripetal fibers, whose trophic centers are located in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent] or secretomotor fibers as is the case for glands; these are precisely the facts which lead to suppose that the Glomus caroticum is a sensory organ.” A few pages down, de Castro wrote: “ The Glomus represents an organ with multiple receptors furnished with specialized receptor cells like those of other sensory organs [taste buds?]…As a plausible hypothesis we propose that the Glomus caroticum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that, possibly by a reflex mechanism would have an effect on the functional activity of other organs… Therefore, the sensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cells of the organ, which, as their structure suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers.” In our article we will recreate the experiments that allowed Fernando de Castro to reach this first conclusion. Also, we will scrutinize the natural endowments and the scientific knowledge that drove de Castro to make the triple hypotheses: the CB as chemoreceptor (variations in blood composition), as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemic reflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we will complete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functioning of this arterial chemoreceptor.

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          Most cited references38

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          Carotid body chemoreceptors: from natural stimuli to sensory discharges.

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            Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas.

            Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes. About 30% of PCCs and PGLs are currently believed to be caused by germline mutations and several novel susceptibility genes have recently been discovered. The clinical presentation, including localization, malignant potential, and age of onset, varies depending on the genetic background of the tumors. By reviewing more than 1700 reported cases of hereditary PCC and PGL, a thorough summary of the genetics and clinical features of these tumors is given, both as part of the classical syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease, neurofibromatosis type 1, and succinate dehydrogenase-related PCC-PGL and within syndromes associated with a smaller fraction of PCCs/PGLs, such as Carney triad, Carney-Stratakis syndrome, and MEN1. The review also covers the most recently discovered susceptibility genes including KIF1Bβ, EGLN1/PHD2, SDHAF2, TMEM127, SDHA, and MAX, as well as a comparison with the sporadic form. Further, the latest advances in elucidating the cellular pathways involved in PCC and PGL development are discussed in detail. Finally, an algorithm for genetic testing in patients with PCC and PGL is proposed.
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              The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases.

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                Author and article information

                Contributors
                Journal
                Front Neuroanat
                Front Neuroanat
                Front. Neuroanat.
                Frontiers in Neuroanatomy
                Frontiers Media S.A.
                1662-5129
                13 March 2014
                12 May 2014
                2014
                : 8
                : 25
                Affiliations
                [1] 1Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid Valladolid, España
                [2] 2CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Facultad de Medicina, Universidad de Valladolid Valladolid, España
                Author notes

                Edited by: Fernando de Castro, Hospital Nacional de Parapléjicos – Servicio de Salud de Castilla-La Mancha, Spain

                Reviewed by: José A. Armengol, University Pablo de Olavide, Spain; Ping Liu, University of Connecticut Health Center, USA

                *Correspondence: Constancio Gonzalez, Departamento de Bioqumica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47005 Valladolid, España e-mail: constanc@ 123456ibgm.uva.es

                This article was submitted to the journal Frontiers in Neuroanatomy.

                Article
                10.3389/fnana.2014.00025
                4026738
                2401f741-af61-4fce-8dfe-31f0d74e82ef
                Copyright © 2014 Gonzalez, Conde, Gallego-Martín, Olea, Gonzalez-Obeso, Ramirez, Yubero, Agapito, Gomez-Niño, Obeso, Rigual and Rocher.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 February 2014
                : 03 April 2014
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 50, Pages: 16, Words: 0
                Categories
                Neuroscience
                Review Article

                Neurosciences
                fernando de castro,carotid body,arterial chemoreceptorss,sensory physiology,ion channels,transduction cascade

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