title: Hypoxia induces adenosine release from the rat carotid body.
abstract: The effect of hypoxia on the release of adenosine was studied in vitro in the rat whole carotid body (CB) and compared with the effect of hypoxia (2%, 5% and 10% O(2)) on adenosine concentrations in superior cervical ganglia (SCG) and carotid arteries. Moderate hypoxia (10% O(2)) increased adenosine concentrations released from the CBs by 44%, but was not a strong enough stimulus to evoke adenosine release from SCG and arterial tissue. The extracellular pathways of adenosine production in rat CBs in normoxia and hypoxia were also investigated. S-(p-nitrobenzyl)-6-thioinosine (NBTI) and dipyridamole were used as pharmacological tools to inhibit adenosine equilibrative transporters (ENT) and alpha,beta-methylene ADP (AOPCP) to inhibit ecto-5'-nucleotidase. Approximately 40% of extracellular adenosine in the CB came from the extracellular catabolism of ATP, under both normoxic and hypoxic conditions. Low pO(2) triggers adenosine efflux through activation of NBTI-sensitive ENT. This effect was only apparent in hypoxia and when adenosine extracellular concentrations were reduced by the blockade of ecto-5'-nucleotidase. We concluded that CB chemoreceptor sensitivity could be related to its low threshold for the release of adenosine in response to hypoxia here quantified for the first time.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, New University of Lisbon, Campo Mártires da Pátria 130, 1169-056 Lisbon, Portugal.
authors.forename: Sílvia V
authors.initials: SV
authors.lastname: Conde
authors.forename: Emília C
authors.initials: EC
authors.lastname: Monteiro
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors; D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; D051381:Rats; D017208:Rats, Wistar; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; C444719:adenosine transporter; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D013868:Thioinosine; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D015720:5'-Nucleotidase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine