Fernando de Castro and the discovery of the arterial chemoreceptors

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.

Sensory Processing and Integration at the Carotid Body Tripartite Synapse: Neurotransmitter Functions and Effects of Chronic Hypoxia

“…In mammals, the main peripheral chemoreceptor organs are the carotid bodies (CBs), which contain O 2 - and CO 2 /H + -sensitive detectors known as glomus or type I cells (Gonzalez et al, 1994 ; Peers and Buckler, 1995 ; López-Barneo et al, 2016 ). While the chemoreceptive properties of the CB have been well established over much of the last century (Gonzalez et al, 2014 ), current views consider the CBs as general metabolic sensors capable of detecting not only the respiratory gases and blood acidity, but also blood glucose and circulating insulin levels (López-Barneo, 2003 ; Conde et al, 2014 ; Thompson et al, 2016 ).…”

The Cajal School in the Peripheral Nervous System: The Transcendent Contributions of Fernando de Castro on the Microscopic Structure of Sensory and Autonomic Motor Ganglia

“…After 1925, Fernando de Castro combined his work on autonomic ganglia with the study on the innervation of the aorto-carotid region. This work fundamentally changed the field (for specific reviews in this subject, see de Castro, 2009 ; González et al, 2014 —included in this current Special Research Topic; Figure 4A ). In the attempts to prove his hypothesis that neurons located in the carotid bodies act as sensory chemoreceptors that detect changes in the chemical composition of circulating blood, Fernando de Castro took an alembicated experimental way that should pass through… the orthosympathetic ganglia!…”

“…Civil war erupted in Spain in 1936 and fighting reached Madrid towards the end of that year. Fernando de Castro, being in charge of protecting the equipment and collections of the Cajal Institute, became fully occupied in protecting the Institute from literal disappearance during the almost 3 years (1936–1939) that the Spanish Civil War ravaged Madrid (de Castro, 2009 ; De Carlos and Pedraza, 2014 ; González et al, 2014 ). In the mean time the Belgian physio-pharmacologist Corneille Heymans (1892–1968) took advantage of the opportunity and won the race to functionally demonstrate the origin in the carotid body of the chemical reflexes.…”

Vasoactive Intestinal Polypeptide in the Carotid Body—A History of Forty Years of Research. A Mini Review

“…The history of studies on the carotid body reaches back to the year 1743, when this organ was described for the first time [8]. However, the most accurate investigations of the carotid body were performed only in the 20th century.…”