Differential Changes in Dopamine D₂- and D₁-Receptor mRNA Levels Induced by Hypoxia in the Arterial Chemoreflex Pathway Organs in One-Day-Old and Adult Rabbits

Abstract

This study determined: (1) whether dopamine (DA) D₂-receptor (R) and D₁-R mRNA levels in the carotid body (CB), petrosal ganglion (PG) and superior cervical ganglion (SCG) are modulated by hypoxia; (2) the role of hypoxia intensity and exposure duration, and (3) whether the pattern of modulation differs between newborn (1-day-old) and adult rabbits. Rabbits were exposed to five F_iO₂ conditions: 21% (control); 15%/6 h; 15%/24 h; 8%/6 h and 8%/24 h. D₂- and D₁-R mRNA expression levels were calculated for each hypoxia condition relative to control using RT-PCR analysis. In the CB of 1-day-old rabbits, D₂- and D₁-R transcript levels increased and decreased after exposure to 15 and 8% O₂, respectively. In the adult CB, D₂- and D₁-R transcript levels decreased independently of hypoxia intensities. Only changes in D₁-R mRNA levels were dependent on exposure time. In the PG, both hypoxia intensities decreased the D₂-R transcript levels in 1-day-old and adult rabbits; but for the D₁-R mRNA levels, hypoxia decreased its level in 1-day-old rabbits and increased it in adults regardless of exposure duration. In the SCG, hypoxia had no determinant effect on the D₂-R mRNA levels either in newborn or adult rabbits while it induced a decrease of D₁-R transcript levels in 1-day-old rabbits and an increase in adult rabbits. It is concluded that hypoxia affects DA D₂- or D₁-R mRNA levels in the chemoreflex pathway in an age-dependent and site-specific manner.

Distribution of voltage‐gated potassium and hyperpolarization‐activated channels in sensory afferent fibers in the rat carotid body

“…The immunoreactivity for HCN2 is of interest because HCN2 is modulated by cAMP. Transmitters such as dopamine which is released from the glomus cells may alter cAMP levels in the terminals via postsynaptic D1/D2 receptors (Bairam et al 2003; Czyzyk-Krzeska, 1992; Kline et al, 2002) and thus regulate the terminal membrane potential through HCN2. This is in line with the modulatory role of dopamine proposed in a recent review (Iturriaga and Alcayaga, 2004).…”

Neonatal Environment and Neuroendocrine Programming of the Peripheral Respiratory Control System

“…Furthermore, newborn rabbits exposed to 8% O 2 for 24 hours immediately after birth show a decrease in dopamine D 2 receptors mRNA expression in comparison to the levels measured in normoxic pups (Fig. 3) [59]. Together, these observations clearly indicate that exposing carotid bodies to excessive or insufficient O 2 -related stimulation causes significant alterations in carotid body oxygen sensitivity and that changes in dopaminergic neurotransmission contribute (at least in part) to the functional phenotype subsequently observed in these animals.…”

Hypoxia-induced transcription of dopamine D3 and D4 receptors in human neuroblastoma and astrocytoma cells

“…In contrast, hypoxia profoundly increased DRD2 mRNA in the rostral nucleus tractus solitarius at all time points investigated [17]. A study conducted on rabbit brains also revealed that hypoxic expression patterns of DRD1 and DRD2 in different brain areas are far from being uniform [18]. Moreover, widely accepted concepts like induction of the tyrosine hydroxylase gene by hypoxia [19] have been challenged by recent studies finding practically unaltered or slightly decreased transcript and protein levels upon hypoxia [20,21].…”