Hypoxia induces adenosine release from the rat carotid body.
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.
Conde
Sílvia V
SV
Department of Pharmacology, Faculty of Medical Sciences, New University of Lisbon, Campo Mártires da Pátria 130, 1169-056 Lisbon, Portugal.
Monteiro
Emília C
EC
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
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