Histaminergic and dopaminergic traits in the human carotid body

Lazarov, Nikolai; Reindl, Sebastian; Fischer, Florian; Gratzl, Manfred

doi:10.1016/j.resp.2008.10.016

Cited by 25 publications

(17 citation statements)

References 29 publications

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“…Tissue sections were stained with selective antibodies against TH, nestin or GFAP to identify characteristic glomus (type I) and sustentacular (type II) cells, respectively. We found clusters of TH+ cells in the human CB, but as previously reported (Lazarov et al 2009) the number of these cells was surprisingly low (∼1–2% of the cell population with DAPI‐stained nuclei) in comparison with routinely observed values (>20%) in CBs from adult rodents (Ortega‐Sáenz et al 2006; Pardal et al 2007). However, the actual number of human glomus cells was clearly higher (>10%) as demonstrated by the staining of sections with antibodies against DDC, which also showed the typical appearance of clusters of glomus cells (Fig.…”

Section: Resultssupporting

confidence: 56%

Cellular properties and chemosensory responses of the human carotid body

Ortega-Sáenz

Pardal

Levitsky

et al. 2013

The Journal of Physiology

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Key points• The carotid body (CB) is a key chemoreceptor organ that mediates the hyperventilatory response to hypoxia, and contributes to the process of acclimatisation to chronic hypoxaemia.• Knowledge of CB physiology at the cellular and molecular levels has advanced considerably in recent times thanks to studies on lower mammals; however, information on humans is practically absent. Here we describe the properties of human CB cells in slice preparations or after enzymatic dispersion.• Besides glomus (type I) and glia-like, sustentacular (type II) cells, adult human CBs contain nestin-positive neural progenitor cells. The human CB also expresses high levels of glial cell line-derived neurotrophic factor. These properties are maintained at an advanced age.• Human glomus cells contain a relatively high density of voltage-dependent Na + , Ca 2+ and K + channels. Membrane depolarisation with high extracellular K + induces an increase of cytosolic [Ca 2+ ] and quantal catecholamine release.• Human glomus cells are responsive to hypoxia and hypoglycaemia, both of which induce an increase in cytosolic [Ca 2+ ] and transmitter release. Chemosensory responses of glomus cells are also preserved at an advanced age.• These findings on the cellular and molecular physiology of the CB provide novel perspectives for the systematic study of pathologies involving this organ in humans.Abstract The carotid body (CB) is the major peripheral arterial chemoreceptor in mammals that mediates the acute hyperventilatory response to hypoxia. The CB grows in response to sustained hypoxia and also participates in acclimatisation to chronic hypoxaemia. Knowledge of CB physiology at the cellular level has increased considerably in recent times thanks to studies performed on lower mammals, and rodents in particular. However, the functional characteristics of human CB cells remain practically unknown. Herein, we use tissue slices or enzymatically dispersed cells to determine the characteristics of human CB cells. The adult human CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). We found that GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. qualitatively similar to those reported in lower mammals. These cells responded to hypoxia with an external Ca 2+ -dependent increase of cytosolic Ca 2+ and quantal catecholamine secretion, as reported for other mammalian species. Interestingly, human glomus cells are also responsive to hypoglycaemia and together these two stimuli can potentiate each other's effects. The chemosensory responses of glomus cells are also preserved at an advanced age. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

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Section: Resultssupporting

confidence: 56%

Cellular properties and chemosensory responses of the human carotid body

Ortega-Sáenz

Pardal

Levitsky

et al. 2013

The Journal of Physiology

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“…We have found the typical clusters of TH+ cells in the human CB ( Fig. 16.1d ), although as previously reported (Lazarov et al 2009 ), the number of these cells was surprisingly low (~1-2 % of the cell population) in comparison with values (>20 %) described in rodent CBs (Ortega-Saenz et al 2006 ;Pardal et al 2007 ). However, the actual number of human glomus cells is clearly higher (>10 %) than that revealed by TH immunofl uorescence, as demonstrated by the staining of sections with antibodies against DDC, which also shows the typical appearance of clusters of glomus cells (Fig.…”

Section: Structure and Gdnf Content Of The Human Cbsupporting

confidence: 79%

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

Ortega-Sáenz

Villadiego

Pardal

et al. 2015

Advances in Experimental Medicine and Biology

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The carotid body (CB) is a polymodal chemoreceptor that triggers the hyperventilatory response to hypoxia necessary for the maintenance of O(2) homeostasis essential for the survival of organs such as the brain or heart. Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia, acidosis and, although less generally accepted, hypoglycemia. Current knowledge on CB function is mainly based on studies performed on lower mammals, but the information on the human CB is scant. Here we describe the structure, neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of CBs dissected from human cadavers. The adult CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. As reported for other mammalian species, glomus cells responded to hypoxia by external Ca(2+)-dependent increase of cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also responsive to hypoglycemia and together the two stimuli, hypoxia and hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of glomus cells are also preserved at an advanced age. Interestingly, a neurogenic niche similar to that recently described in rodents is also preserved in the adult human CB. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

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“…Immunohistochemically, immunoreactivity for tyrosine hydroxylase (TH; EC1.14.16.2), the rate-limiting enzyme of catecholamine biosynthesis, was widely observed in the glomus cells (Wang et al 1991;Oomori et al 1994;Wang and Bisgard 2002). Additionally, it is reported that dopamine D 2 receptor mRNA is expressed in glomus cells of rat carotid body in a study using ISH (Czyzyk-Krzeska et al 1992b), and that immunoreactivity for dopamine D 2 receptor was observed in glomus cells and nerve fiber of human carotid body (Lazarov et al 2009). On the other hand, it is suggested, again using ISH, that dopamine D 1 receptor is absent in glomus cells because dopamine D 1 receptor mRNA was not detected in glomus cells of rat carotid body (Czyzyk-Krzeska et al 1992b;Gauda 2002).…”

mentioning

confidence: 99%

Short-term Hypoxia Increases Tyrosine Hydroxylase Immunoreactivity in Rat Carotid Body

Kato

Yamaguchi-Yamada

Yamamoto

2010

J Histochem Cytochem.

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S U M M A R Y Neurochemical and morphological changes in the carotid body are induced by chronic hypoxia, leading to regulation of ventilation. In this study, we examined the time courses of changes in immunohistochemical intensity for tyrosine hydroxylase (TH) and cellular volume of glomus cells in rats exposed to hypoxia (10% O 2 ) for up to 24 hr. Grayscale intensity for TH immunofluorescence was significantly increased in rats exposed to hypoxia for 12, 18, and 24 hr compared with control rats (p,0.05). The transectional area of glomus cells was not significantly different between experimental groups. The TH fluorescence intensity of the glomus cells exhibited a strong negative correlation with the transectional area in control rats (Spearman's ρ 5 20.70). This correlation coefficient decreased with exposure time, and it was lowest for the rats exposed to hypoxia for 18 hr (ρ 5 20.18). The histogram of TH fluorescence intensity showed a single peak in control rats. The peaks were gradually shifted to the right and became less pronounced in hypoxia-exposed rats, suggesting that a hypoxiainduced increase in TH immunoreactivity occurred uniformly in glomus cells. In conclusion, this study demonstrates that short-term hypoxia induces an increase in TH protein expression in rat carotid body glomus cells. (J Histochem Cytochem 58:839-846, 2010)

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Histaminergic and dopaminergic traits in the human carotid body

Cited by 25 publications

References 29 publications

Cellular properties and chemosensory responses of the human carotid body

Cellular properties and chemosensory responses of the human carotid body

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

Short-term Hypoxia Increases Tyrosine Hydroxylase Immunoreactivity in Rat Carotid Body

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