Carotid Body Chemotransduction

Marcel Dekker, L c. 270 Madison Avenue, New York, New York 10016 

Data support the presence and activity of several neurotransmitters in the carotid body ACh, DA, ATP, substance P (SP), adenosine, NO, to name those most frequently studied. Our interest up to the present has focused primarily on the first two. In the cat carotid body ACh functions as an excitatory neurotransmitter. An overwhelming amount of evidence supports an inhibitory role for DA in the cat carotid body, although xmder certain quite limited conditions exogenously administered DA can excite or give a biphasic response. In the rat ATP appears to play as important an excitatory role as ACh (15). Adenosine and NO appear to play important modulatory roles at least. SP can excite the carotid body, but in the cat this effect can be reduced by the use of cholinergic antagonists (14). It is not uncommon for SP to be coreleased with and modulate the effect of ACh in other tissues under cholinergic control (20,21). 

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Lahiri S, Rumsey WL, Wilson DF, Iturriaga R. Contribution of in vivo microvascular PO2 in the cat carotid body chemotransduction. J Appl Physiol 1993 75 1035-1043. 

Donnelly DF. Are oxygen dependent K channels essential for carotid body chemotransduction Respir Physiol 1997 110(2-3) 211-218. 

Studies by McDonald (4), by Kondo and Iwasa (19), and by us have revealed that all cellular elements involved in carotid body chemotransduction are interconnected by gap junctions. However, all these studies have been done in the rat and we do not know if these findings can be extended to other animal species. There is only one observation showing that an intracellular dye injected into a cat glomus cell spread to its neighbors (3). 

Fitzgerald RS, Shirahata M, Ide T. Further cholinergic aspects of carotid body chemotransduction of hypoxia in cats. J Appl Physiol 1997 82(3) 819-827. 

Fitzgerald RS. Oxygen and carotid body chemotransduction the cholinergic hypothesis Respir Physiol 2000 120(2) 89-104. 

Figure 1 Model of cat carotid body s components thought to he involved in carotid body chemotransduction. NTS nucleus tractus solitarii in the hrainstem PG petrosal ganglion Al, A2a adenosine receptors P2X2 purinoceptor Ml, M2 types of muscarinic receptors N nicotinic receptors Dl, D2 dopamine receptors K potassium channels VGCC voltagegated calcium channels Ach acetylcholine DA dopamine NE norepinephrine SP substance P ATP adenosine triphosphate NO nitric oxide. The glomus cell, embraced by the calyx type sensory afferent fiber, contains several putative neurotransmitters. It is highly unlikely that every glomus cell contains all the listed neurotransmitters. Presumably the neurotransmitter can act wherever the appropriate receptors are located, postsynaptically as well as presynaptically. See text for postulated steps in the release of the neurotransmitters.

C.N. Wyatt et al., 02-sensitive currents in carotid body chemoreceptor cells from normoxic and chronically hypoxic rats and their roles in hypoxic chemotransduction, Proc. Natl. Acad. Sci. USA 92(1995) 295-299. 

Lopez-Bameo J, Lopez-Lopez JR. Urena J, Gonzales C. Chemotransduction in the carotid body K current modulated by PO2 in type I chemoreceptor cells. Science 1989 241 580-582. 

Shirahata M, Fitzgerald RS. Dependency of hypoxic chemotransduction in cat carotid body on voltage-gated calcium channels. J Appl Physiol 1991 71(3) 1062-1069. 

In this model of dopaminergic chemotransduction, the apparent aforementioned paradox may be resolved if one considers that the enhanced catecholamine content and general carotid body hyperplasia xmder chronic hypoxia are associated with an enhanced number of functional chemoreceptor units (composed of at least one glomic cell and one sensitive nerve ending forming a synapse) within the carotid body (Fig. 1). In this pattern, the overall activity of the carotid sinus nerve (which conveys the chemo sensitive information from the carotid body to the brainstem respiratory centers) may be enhanced as well as dopamine content. 

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