Time-dependent changes in dopamine D(2)-receptor mRNA in the arterial chemoreflex pathway with chronic hypoxia.
The hypoxic ventilatory response (HVR) can be modulated by dopamine D(2)-receptors (D(2)-R) in both the carotid body arterial chemoreceptors and the nucleus tractus solitarius (NTS), the primary synapse site of carotid body afferents. We hypothesized that chronic hypoxia alters D(2)-R gene expression to initiate changes in D(2)-R modulation of the HVR and enhance ventilatory acclimatization to hypoxia. Thus, we used a competitive reverse transcription-polymerase chain reaction (RT-PCR) method to quantify changes in D(2)-R mRNA levels in the rat carotid body and NTS after 0, 6, 12, 24, 48, or 168 h of hypobaric hypoxia (P(IO(2))=80 Torr). In the rostral NTS, hypoxia significantly increased D(2)-R mRNA at all time points. In the caudal NTS, D(2)-R mRNA levels initially increased in response to hypoxia and then significantly decreased to 71+/-5% and 71+/-6% of control after 48 and 168 h of hypoxia, respectively. In the carotid body, D(2)-R mRNA levels significantly decreased to 59+/-2% of control after 48 h of hypoxia; however, they significantly increased to 274+/-22% of control after 168 h. These results suggest that changes in D(2)-R mRNA in the arterial chemoreflex pathway and corresponding changes at the protein and signaling levels may contribute to the time-dependent changes in ventilation observed with chronic hypoxia. Specifically, decreased carotid body inhibition by D(2)-R could increase the HVR after 2 days of hypoxia.
Huey
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Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA. khuey@uci.edu
Powell
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D000818:Animals; D002344:Carotid Body / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D010100:Oxygen