期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms21155434
关键词
carotid body; dopamine; sulpiride; purinergic signalling; type II cells; petrosal neurons
资金
- Canadian Institutes of Health Research [MOP 142469]
- Natural Sciences and Engineering Research Council of Canada
Dopamine (DA) is a well-studied neurochemical in the mammalian carotid body (CB), a chemosensory organ involved in O(2)and CO2/H(+)homeostasis. DA released from receptor (type I) cells during chemostimulation is predominantly inhibitory, acting via pre- and post-synaptic dopamine D2 receptors (D2R) on type I cells and afferent (petrosal) terminals respectively. By contrast, co-released ATP is excitatory at postsynaptic P2X2/3R, though paracrine P2Y2R activation of neighboring glial-like type II cells may boost further ATP release. Here, we tested the hypothesis that DA may also inhibit type II cell function. When applied alone, DA (10 mu M) had negligible effects on basal [Ca2+](i)in isolated rat type II cells. However, DA strongly inhibited [Ca2+](i)elevations (Delta[Ca-i(2+])) evoked by the P2Y2R agonist UTP (100 mu M), an effect opposed by the D2/3R antagonist, sulpiride (1-10 mu M). As expected, acute hypercapnia (10% CO2; pH 7.4), or high K+(30 mM) caused Delta[Ca2+](i)in type I cells. However, these stimuli sometimes triggered a secondary, delayed Delta[Ca2+](i)in nearby type II cells, attributable to crosstalk involving ATP-P2Y2R interactions. Interestingly sulpiride, or DA store-depletion using reserpine, potentiated both the frequency and magnitude of the secondary Delta[Ca2+](i)in type II cells. In functional CB-petrosal neuron cocultures, sulpiride potentiated hypercapnia-induced Delta[Ca2+](i)in type I cells, type II cells, and petrosal neurons. Moreover, stimulation of type II cells with UTP could directly evoke Delta[Ca2+](i)in nearby petrosal neurons. Thus, dopaminergic inhibition of purinergic signalling in type II cells may help control the integrated sensory output of the CB during hypercapnia.
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