ReviewNeurotransmission in the carotid body: transmitters and modulators between glomus cells and petrosal ganglion nerve terminals
Introduction
The carotid body (CB) is the main arterial chemoreceptor that senses the arterial levels of PO2, PCO2 and pH, playing an important role in respiratory, cardiovascular and neurohumoral regulation. The CB consists of glomus (type I) cells synaptically connected to the nerve terminals of petrosal ganglion (PG) neurons and engulfed by sustentacular (type II) cells, where glomus cells are the primary transduction loci and PG neurons convey chemosensory activity to the central nervous system (Fig. 1). In response to hypoxia, hypercapnia and acidosis, chemosensory discharges in the carotid sinus nerve increase [15], [16], [24]. The most accepted model of chemoreception proposes that transduction of natural stimuli by glomus cells increase its intracellular [Ca2+], which mediates the exocytotic release of one (or more) transmitter(s). This transmitter, acting on specific post-synaptic receptors, increases the rate of discharge in nerve fibers of PG neurons projecting to the CB [16], [24]. Glomus cells contain several molecules, such as catecholamines, acetylcholine (ACh), adenosine nucleotides and peptides, that are candidates to act as excitatory transmitters in the junctions between glomus cells and nerve terminals [15], [24]. A high degree of co-localization for amine-synthesizing enzymes (tyrosine hydroxylase, dopamine-β-hydroxylase and choline acetyltransferase), and substance P and met-encephalin have been found in the glomus cells of cat CB [55]. Therefore, it is likely that glomus cells store and release more than one excitatory transmitter in response to natural stimuli. In this review, we will examine this possibility, focusing on the role played by ACh, adenosine 5′-triphosphate (ATP) and dopamine (DA) in CB chemoreception, with special emphasis on the their possible interactions.
Section snippets
Acetylcholine
ACh meets most of the criteria to be considered an excitatory transmitter between the glomus cells and the nerve terminals [19]. ACh is present in the CB and its content remains unchanged after the section of the carotid sinus nerve [17] or the removal of the superior cervical ganglion [25]. Choline acetyltransferase, the enzyme responsible for ACh synthesis, is localized in rat [42], cat and rabbits glomus cells [54], and a high affinity, sodium-dependent choline uptake mechanism has been
Adenosine 5′-triphosphate
Large amounts of adenine nucleotides have been found by fluorescence microscopy in glomus cells, stored within specific granules in addition to catecholamines and proteins [10]. Intracarotid injections of adenosine and ATP evoke a dose-dependent increase in chemosensory discharge in the cat CB [40], [41], [45], but adenine, inosine, guanosine, cytidine and uridine have no appreciable effect on chemoreceptor discharge [41]. These results suggest that ATP exerts its action through its hydrolysis
Dopamine
Dopamine (DA) is the predominant catecholamine (CA) synthesized, stored in dense-cored vesicle, and taken-up by glomus cells of several species [24]. The presence of dopaminergic neurons [32], [33] as well as mRNA for D2 receptors [8], [11] has been shown in a population of PG neurons. The proposition that DA is the excitatory transmitter in the CB was strongly supported by the observation that hypoxia produces CA release from the CB [24] and from isolated glomus cells [51]. In fact, after
Conclusion
Experimental evidence obtained from preparations, like the isolated PG, cultured PG neurons, and co-cultures of PG neurons and CB cells suggest that ACh and ATP could mediate excitatory transmission in the CB. In addition, DA release from the glomus cells appears to act as a modulator of the chemosensory responses in most species, but may play a more critical role in the excitatory transmission in the CB of some species (i.e., rabbit).
Acknowledgements
This work was supported by grants 1990030 and 1030330 from the National Fund for Scientific and Technological Development of Chile (FONDECYT).
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