The aim of this study was to identify the mechanisms that regulate dopamine release (DA(r)) by the hypoxic carotid body (CB) during development. CBs sampled from adult (n = 58) and 10-day-old (n = ...53) rabbits were incubated for 1 h in a medium equilibrated with 8% O(2) in N(2) without or in the presence of the specific DA D(2) receptor antagonist domperidone, 0.01, 0.1 and 1 microM. DA and its major metabolite DOPAC were measured in the CB (DA(CB)) and in the medium (DA(r)) by HPLC+ED. In adults, each concentration of domperidone significantly decreased DA(CB) and increased DA(r), compared with control (p < 0.01). In contrast, in 10-day old, only the 1 microM domperidone concentration decreased DA(CB) and increased DA(r) compared with control (p < 0.001). The data show that domperidone increases CB DA(r) in response to hypoxia in a concentration- and age-dependent manner and suggest this response depends, in part, on the functional maturation of CB DA D(2) receptors.
Dopamine (DA) release (r) from the carotid body (CB) is thought to be modulated by feedback inhibition mediated by DA D
2 autoreceptors. We tested the hypothesis that CB DA
r is autoregulated in a ...concentration and age dependent manner. Using an in vitro CB infusion model Bairam, A., Marchal, F., Cottet-Emard, J.M., Basson, H., Pequignot, J.M., Hascoet, J.M., Lahiri, S., 1996b. Effects of hypoxia on carotid body dopamine content and release in developing rabbits. J. Appl. Physiol. 80, 20–24., we evaluated under unstimulated conditions the effects of 0.001, 0.01, 0.1, 1.0 and 10.0 μM of the specific DA D
2 receptor antagonist domperidone on CB DA
r in adult rabbits. In 10-day-old rabbit pups, concentrations of 0.01, 0.1, 1.0 μM were studied. In adult CBs, domperidone increased DA
r in a concentration-dependent manner. DA
r (pmol/h) was significantly greater compared to control (without domperidone) starting at a domperidone concentration of 0.1 μM (
P<0.01). In 10-day-old pup CBs, 1.0 μM domperidone was required to produce a significant increase of DA
r (pmol/h) compared to control (
P<0.005). However, control DA
r (as % of total catecholamine) was about 40%; significantly higher than 24% observed in adult CBs (
P<0.001). We conclude that in rabbit CB, DA
r is controlled by an autoreceptor mechanism in a concentration-dependent manner and this mechanism is less developed in pups than in adults.
