The identification of dopamine in the rabbit’s carotid body

1968 ◽  
Vol 170 (1019) ◽  
pp. 195-203 ◽  
Keyword(s):  
Carotid Body ◽  
Model System ◽  
Type I ◽  
Histochemical Technique ◽  
High Concentration ◽  
Metabolic Intermediate ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Perivascular Nerves ◽  
I Cells

Application of the Falck & Hillarp histochemical technique to the rabbit carotid body reveals three fluorescent structures: brilliantly fluorescent Type I cells, varicose perivascular nerves, and weakly fluorescent non-varicose fibres. The Type I cell fluorescence is similar to that of a dopamine model system and has the appropriate activation and emission maxima. A catecholamine, identified as dopamine, has been extracted from homogenized carotid bodies, and estimated by the trihydroxyindole procedure. The concentration of the dopamine in the carotid body is estimated to be 20 to 40 μ g/g. This is very much greater than that of the noradrenaline present, of which there is about 1·5 μ g/g. The fluorescence of the Type I cells is attributed to the dopamine and it is suggested that the amine may be granule-bound. The unusually high concentration of dopamine could imply that it is not merely a metabolic intermediate in the carotid body.

Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice

2002 ◽  
Vol 282 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
L. He ◽  
J. Chen ◽  
B. Dinger ◽  
K. Sanders ◽  
K. Sundar ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Nadph Oxidase ◽  
Carotid Body ◽  
Gene Knockout ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Marker Antigen ◽  
I Cells

Various heme-containing proteins have been proposed as primary molecular O2 sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91 phox ) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O2-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K+currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca2+ concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91 phox gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O2 sensor in arterial chemoreception.

scholarly journals Immunohistochemical Characteristics of the Human Carotid Body in the Antenatal and Postnatal Periods of Development

2021 ◽  
Vol 22 (15) ◽  
pp. 8222
Author(s):  
Dmitry Otlyga ◽  
Ekaterina Tsvetkova ◽  
Olga Junemann ◽  
Sergey Saveliev
Keyword(s):  
Tyrosine Hydroxylase ◽  
Carotid Body ◽  
Nerve Fibers ◽  
Individual Development ◽  
Endocrine Function ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
I Cells ◽  
Human Carotid

The evolutionary and ontogenetic development of the carotid body is still understudied. Research aimed at studying the comparative morphology of the organ at different periods in the individual development of various animal species should play a crucial role in understanding the physiology of the carotid body. However, despite more than two centuries of study, the human carotid body remains poorly understood. There are many knowledge gaps in particular related to the antenatal development of this structure. The aim of our work is to study the morphological and immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. We investigated the human carotid bodies from 1 embryo, 20 fetuses and 13 adults of different ages using samples obtained at autopsy. Immunohistochemistry revealed expression of βIII-tubulin and tyrosine hydroxylase in the type I cells and nerve fibers at all periods of ontogenesis; synaptophysin and PGP9.5 in the type I cells in some of the antenatal cases and all of the postnatal cases; 200 kDa neurofilaments in nerve fibers in some of the antenatal cases and all of the postnatal cases; and GFAP and S100 in the type II cells and Schwann cells in some of the antenatal cases and all of the postnatal cases. A high level of tyrosine hydroxylase in the type I cells was a distinctive feature of the antenatal carotid bodies. On the contrary, in the type I cells of adults, the expression of tyrosine hydroxylase was significantly lower. Our data suggest that the human carotid body may perform an endocrine function in the antenatal period, while in the postnatal period of development, it loses this function and becomes a chemosensory organ.

scholarly journals Gene expression and function of adenosine A2A receptor in the rat carotid body

2000 ◽  
Vol 279 (2) ◽  
pp. L273-L282 ◽  
Author(s):  
Shuichi Kobayashi ◽  
Laura Conforti ◽  
David E. Millhorn
Keyword(s):  
Carotid Body ◽  
Cellular Response ◽  
Cell Voltage ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
Immunohistochemical Studies ◽  
I Cells ◽  
Receptor Mrnas

The present study was undertaken to determine whether rat carotid bodies express adenosine (Ado) A2A receptors and whether this receptor is involved in the cellular response to hypoxia. Our results demonstrate that rat carotid bodies express the A2A and A2B Ado receptor mRNAs but not the A1 or A3 receptor mRNAs as determined by reverse transcriptase-polymerase chain reaction. In situ hybridization confirmed the expression of the A2A receptor mRNA. Immunohistochemical studies further showed that the A2A receptor is expressed in the carotid body and that it is colocalized with tyrosine hydroxylase in type I cells. Whole cell voltage-clamp studies using isolated type I cells showed that Ado inhibited the voltage-dependent Ca2+ currents and that this inhibition was abolished by the selective A2A receptor antagonist ZM-241385. Ca2+ imaging studies using fura 2 revealed that exposure to severe hypoxia induced elevation of intracellular Ca2+ concentration ([Ca2+]i) in type I cells and that extracellularly applied Ado significantly attenuated the hypoxia-induced elevation of [Ca2+]i. Taken together, our findings indicate that A2A receptors are present in type I cells and that activation of A2Areceptors modulates Ca2+ accumulation during hypoxia. This mechanism may play a role in regulating intracellular Ca2+homeostasis and cellular excitability during hypoxia.

Interactions between hypoxia and hypercapnic acidosis on calcium signaling in carotid body type I cells

2000 ◽  
Vol 279 (1) ◽  
pp. L36-L42 ◽  
Author(s):  
Leonardo L. T. Dasso ◽  
Keith J. Buckler ◽  
Richard D. Vaughan-Jones
Keyword(s):  
Carotid Body ◽  
Neonatal Rat ◽  
Single Type ◽  
Type I ◽  
Hypercapnic Acidosis ◽  
Body Type ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
I Cells

The effects of hypercapnic acidosis and hypoxia on intracellular Ca2+concentration ([Ca2+]i) were determined with Indo 1 in enzymatically isolated single type I cells from neonatal rat carotid bodies. Type I cells responded to graded hypoxic stimuli with graded [Ca2+]i rises. The percentage of cells responding was also dependent on the severity of the hypoxic stimulus. Raising CO2 from 5 to 10 or 20% elicited a significant increase in [Ca2+]i in the same cells as those that responded to hypoxia. Thus both stimuli can be sensed by each individual cell. When combinations of hypoxic and acidic stimuli were given simultaneously, the responses were invariably greater than the response to either stimulus given alone. Indeed, in most cases, the response to hypercapnia was slightly potentiated by hypoxia. These data provide the first evidence that the classic synergy between hypoxic and hypercapnic stimuli observed in the intact carotid body may, in part, be an inherent property of the type I cell.

Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase in type I cells of carotid body

1995 ◽  
Vol 78 (5) ◽  
pp. 1904-1909 ◽  
Author(s):  
W. Kummer ◽  
H. Acker
Keyword(s):  
Hydrogen Peroxide ◽  
Carotid Body ◽  
Oxygen Sensor ◽  
Neutrophil Granulocytes ◽  
Type I ◽  
Body Type ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Sensor Protein ◽  
I Cells

We demonstrate, by means of immunohistochemistry, that type I cells of human, guinea pig, and rat carotid bodies react with antisera raised against the subunits p22phox, gp91phox, p47phox, and p67phox of the NAD(P)H oxidase isolated from human neutrophil granulocytes. The findings support previous photometric studies that indicate that carotid body type I cells possess a putative oxygen sensor protein that is similar to the neutrophil NAD(P)H oxidase and consists of a hydrogen peroxide generating low-potential cytochrome b558 with cofactors regulating the electron transfer to oxygen.

Carotid Body Chemoreceptors: Physiology, Pathology, and Implications for Health and Disease

2021 ◽  
Author(s):  
Rodrigo Iturriaga ◽  
Julio Alcayaga ◽  
Mark W. Chapleau ◽  
Virend K Somers
Keyword(s):  
Carotid Body ◽  
Metabolic Diseases ◽  
Ionic Channels ◽  
Type I ◽  
Peripheral Chemoreceptor ◽  
Type I Cells ◽  
Obstructive Sleep ◽  
Carotid Body Chemoreceptors ◽  
Respiratory Gases ◽  
I Cells

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2, and pH, eliciting reflex ventilatory, cardiovascular and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiologic responses, and its role in maintaining health and potentiating disease. Emphasis will be placed on: i) Transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ionic channels; ii) Synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; iii) Integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and iv) The contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension and metabolic diseases, and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.

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