Abstract
Background: The carotid body (CB) plays a critical role in oxygen sensing; however, the role of glutamatergic signaling in the CB response to hypoxia remains uncertain. We previously found that functional multiple glutamate transporters and inotropic glutamate receptors (iGluRs) are expressed in the CB. The aim of this present research is to investigate the expression of group I metabotropic glutamate receptors (mGluRs) (mGluR1 and 5) in the CB and its physiological function in rat CB response to acute hypoxia.Methods: RT-PCR and immunostaining were conducted to examine the mRNA and protein expression of group I mGluRs in the human and rat CB. Immunofluorescence staining was performed to examine the cellular localization of mGluR1 in the rat CB. In vitro carotid sinus nerve (CSN) discharge recording was performed to detect the physiological function of mGluR1 in CB response to acute hypoxia.Results: We found that (1) mRNAs of mGluR1 and 5 were both expressed in the human and rat CB. (2) mGluR1 protein rather than mGluR5 protein was present in rat CB. (3) mGluR1 was distributed in type I cells of rat CB. (4) Activation of mGluR1 inhibited the hypoxia-induced enhancement of CSN activity (CSNA), as well as prolonged the latency time of CB response to hypoxia. (5) The inhibitory effect of mGluR1 activation on rat CB response to hypoxia could be blocked by GABAB receptor antagonist.Conclusion: Our findings reveal that mGluR1 in CB plays a presynaptic feedback inhibition on rat CB response to hypoxia.
Highlights
Oxygen sensing mediated by central and peripheral chemoreceptors is essential for survival of multicellular organisms
We found that exposure of rats to cyclic intermittent hypoxia (CIH) alters the expression of some of these molecules. inotropic glutamate receptors (iGluRs) in the Carotid body (CB) are functional because blockading with the N-methyl-D-aspartate receptors (NMDARs) antagonist MK801 reduces endothelin-induced carotid sinus nerve (CSN) activity (CSNA) (Liu et al, 2018)
Rat brain sections with intense immunoreactive mGluR1 (Figure 2D) or mGluR5 (Figure 2E) were used as positive controls. These results indicate that mGluR1 protein rather than mGluR5 protein is present in rat CB
Summary
Oxygen sensing mediated by central and peripheral chemoreceptors is essential for survival of multicellular organisms. Evidence supports that the type I glomus cells, as presynaptic neuroendocrine cells, establish synapses with afferent sensory fibers of carotid sinus nerve (CSN) (as postsynaptic nerve endings) (Ortega-Sáenz and López-Barneo, 2020). There is general acceptance that transduction of the hypoxic stimulus in the CB involves closure of O2-sensitive K+ channels, which leads to membrane depolarization of type I cells. This process induces Ca2+-dependent release of neurotransmitters from type I cells; subsequently, the neurotransmitters act on specific postsynaptic receptors on CSN afferent fibers (Chang et al, 2015). Studies show that neurotransmitters acting on non-ionotropic receptors of type I cells provide feedback mechanisms to regulate the CB hypoxia response. The aim of this present research is to investigate the expression of group I metabotropic glutamate receptors (mGluRs) (mGluR1 and 5) in the CB and its physiological function in rat CB response to acute hypoxia
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