Dopamine D2 receptor modulation of carotid body type 1 cell intracellular calcium in developing rats

Abstract

]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 2ϩ ]i response to 90-s hypoxia challenges (PO2 ϳ1-2 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 2ϩ ]i increased ϳ3 to 4-fold over resting [Ca 2ϩ ]i in response to hypoxia. Quinpirole (10 M) significantly blunted the peak [Ca 2ϩ ]i response to hypoxia. Repeat challenge with hypoxia plus 10 M quinpirole in the presence of 10 M sulpiride partially restored the hypoxia [Ca 2ϩ ]i response. In sharp contrast to the older aged group, 10 M 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 2ϩ ]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. dopamine receptors; hypoxia; development; chemoreceptor THE MAIN SENSORS of arterial oxygen level in mammals are the carotid body (CB) chemoreceptors (25). It is widely believed that hypoxia leads to CB type 1 cell depolarization and Ca 2ϩ influx through voltage-gated calcium channels. The rise in intracellular calcium ([Ca 2ϩ ] i ) releases neurotransmitter(s), which are believed to cause firing of action potentials in the adjacent carotid sinus nerve terminals and to act presynaptically on type 1 cell autoreceptors (25). Carotid sinus nerve (CSN) input to brain stem respiratory control nuclei drives the ventilatory response to hypoxia and mediates, at least in part, other defensive responses to hypoxic stress (12, 13, 21-23, 30, 31).In neonates, but not adults, carotid denervation leads to high mortality rates and abnormalities of respiratory control (13,15,18,30,31), suggesting a vulnerable period during mammalian postnatal maturation during which the CB is important for survival and normal maturation of breathing control. Despite their importance in the developing infant, the carotid chemoreceptors have low sensitivity to hypoxia at birth and become more sensitive over the first few days or weeks of life (9,10,14,17,33,36,38), a process termed "resetting." The mechanism(s) underlying resetting are unknown, but some have postulated involvement of inhibitory neuromodulators such as dopamine (DA) (28,29).In rats and rabbits, an age-related increase in O 2 sensitivity occurs at the type 1 cell level (41, 45). Both the [Ca 2ϩ ] i rise and the neurotransmitter (catecholamine) release in response to hypoxia increase with maturation, exhibiting the same time course as CSN response maturation, strongly suggesting that a s...

Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine

“…The monoamines (dopamine and serotonin) are a particular group of neurotransmitters released from the carotid body (Gonzalez et al, 1994) that act presynaptically on type I glomus cells (Zhang et al, 2003;Carroll et al, 2005).…”

“…This is because of the potential involvement of dopamine in neonatal fatality or sudden infant death syndrome. At birth the carotid body chemoreceptors have very low sensitivity to hypoxia and tend to become more sensitive after a couple of days, a process called resetting (Carroll et al, 2005).…”

“…Although the mechanisms of resetting are unknown, research has suggested the involvement of dopamine as a neuromodulator during this process (Carroll et al, 2005).…”

“…But, unlike 5-HT, dopamine acts as an inhibitory neurotransmitter, decreasing the amount of ATP and ACh released to the afferent fibers of the carotid sinus nerve (Carroll et al, 2005).…”

“…Dopamine acting via D2 receptors in the carotid body of both mice and rats has been shown to inhibit the effects of hypoxia, resulting in a decrease in the ventilatory response (Carroll et al, 2005;Prieto-Lloret, 2007). Dopamine receptor agonist/antagonists, as well as transgenic mice have been used to study this.…”