Dopamine D2 receptor modulation of carotid body type 1 cell intracellular calcium in developing rats.
Carotid chemoreceptor type 1 cells release dopamine, which inhibits carotid chemoreceptor activity via dopamine D2 autoreceptors on type 1 cells. Postnatal changes in dopaminergic modulation may be involved in postnatal chemoreceptor development. The present study explores dopaminergic modulation of the intracellular calcium ([Ca(2+)](i)) response to hypoxia in type 1 cells from 1, 3, and 11- to 16-day-old rats. Using fura-2, we studied the effects of quinpirole, a D2 receptor agonist, on type 1 cell [Ca(2+)](i) response to 90-s hypoxia challenges (Po(2) approximately 1-2 mmHg). Cells were sequentially exposed to the following challenges: 1) hypoxia control, 2) hypoxia plus quinpirole, and 3) hypoxia plus quinpirole plus sulpiride (D2 receptor antagonist). In the 11- to 16-day-old group, type 1 cell [Ca(2+)](i) increased approximately 3 to 4-fold over resting [Ca(2+)](i) in response to hypoxia. Quinpirole (10 microM) significantly blunted the peak [Ca(2+)](i) response to hypoxia. Repeat challenge with hypoxia plus 10 microM quinpirole in the presence of 10 microM sulpiride partially restored the hypoxia [Ca(2+)](i) response. In sharp contrast to the older aged group, 10 microM quinpirole had minimal effect on hypoxia response of type 1 cells from 1-day-olds and a small but significant effect at 3 days of age. We conclude that stimulation of dopamine D2 receptors inhibits type 1 cell [Ca(2+)](i) response to hypoxia, consistent with an inhibitory autoreceptor role. These findings suggest dopamine-mediated inhibition and oxygen sensitivity increase with age on a similar time course and do not support a role for dopamine as a major mediator of carotid chemoreceptor resetting.
Carroll
J L
JL
University of Arkansas for Medical Sciences, Department of Pediatrics, Little Rock, AR 72202, USA. carrolljohnl@uams.edu
Boyle
K M
KM
Wasicko
M J
MJ
Sterni
L M
LM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002344:Carotid Body / Q000254:growth & development* / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013469:Sulpiride; D002118:Calcium