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Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells

Gallego-Martin, Teresa and Prieto-Lloret, Jesus and Aaronson, Philip and Rocher, Asuncion and Obeso, Ana (2019) Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells. Antioxidants, 8 (3). p. 62. ISSN 2076-3921

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Abstract

Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gallego-Martin, Teresa
Prieto-Lloret, Jesus
Aaronson, Philip
Rocher, Asuncion
Obeso, Ana
Date: 13 March 2019
Date Type: Publication
Journal or Publication Title: Antioxidants
Volume: 8
Number: 3
Publisher: MDPI AG
Page Range: p. 62
DOI or Unique Handle: 10.3390/antiox8030062
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Uncontrolled Keywords: carotid body, hydrogen sulfide, hypoxia, hydroxycobalamin, oxygen sensing
ISSN: 2076-3921
Official URL: http://dx.doi.org/10.3390/antiox8030062
Article Type: Research Article
Date Deposited: 19 May 2021 18:06
Last Modified: 19 May 2021 18:06
URI: http://d-scholarship.pitt.edu/id/eprint/41112

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