Carotid body neurotransmitters

ATP has been implicated as a neurotransmitter in the peripheral chemoreceptors as a result of hypoxic (Prasad et al., 2001 Buttigieg and Nurse, 2004) and CO2/PH stimulation (Zhang and Nurse, 2004). ATP was presumed to be costored with other classical transmitters (e.g., ACh, dopamine, 5-HT, and GABA in the synaptic vesicles in the chemoreceptor cells (type 1 cells) of the carotid body) (Gonzalez et al., 1994 Zhang et al., 2000). More recently, a direct stimulus-evoked ATP release from the type-1 cells has been demonstrated (Buttigieg and Nurse, 2004), and this release was dependent on extracellular Ca via mainly L-type Ca + channels, blocked by nifedipine (50 pm) and cadmium (50 pm). 

Using the same coculture techniques, glomus cells with petrosal ganglion cells (PGN) and recording from the PGN neurons, it was shown that PGN cells and their terminals responded to hypoxia and CO2/PH and not the PGN cells alone (Zhong et al., 1997 Prasad et al., 2001 Zhang and Nurse, 2004). This means that neurotransmitters released from the glomus cells excited the PGN cells. These transmitters consisted of ATP and ACh. Similar results were obtained by Varas et al. (2003). Recorded intracellularly from identified PGN functionally connected with the carotid body (CB) in vitro, and which responded to CB stimulation by stop... 

Chapter 20, by Shirahata et al., and Chapter 21, by Fitzgerald et al., focus on acetyl choline (ACh) as an excitatory neurotransmitter in the carotid body. Shirahata et al. present evidence for coupling of cholinergic receptors to voltage-gated K" "... 

Gonzalez C, Dinger B, Fidone SJ. Functional significance of chemoreceptor cell neurotransmittes. In Gonzalez C, ed. The Carotid Body Chemoreceptors. New "Vork Springer Austin Landes, 1997 47-64. 

Hess A. Chronically denervated rat carotid bodies. Acta Anat 1977 97 307-316. Hellstrom S. Putative neurotransmitters in the carotid body, mass fiagmentographic studies. Adv Biochem Psychopharmacol 1977 16 257-263. 

Some Neurotransmitter Relationships in the Carotid Body s Response to Hypoxia... 

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.

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). 

Stimulate and DA can inhibit cat carotid body neural output. Second, nicotinic, muscarinic, and dopaminergic receptors act in the cat carotid body as they do elsewhere. Thus, exocytotically released ACh and DA should stimulate and inhibit, respectively, postsynaptic neural traffic in the carotid sinus nerve. PresynapticaUy (i.e., on the glomus cells) the presence of the receptors would suggest that—as in other species— they can regulate by positive/negative feedback their own release from the glomus cells and, perhaps, the release of other neurotransmitters. 

The mammalian carotid body expresses a variety of neurochemicals and their receptors (see Tables 1 and 2). The transmitters expressed in the carotid body can be classified into two major categories conventional and imconventional. The conventional class of neurotransmitters includes those that are stored in vesicles and exert their effect via activation of specific receptors. Examples of this class include catecholamines, acetylcholine, and neuropeptides, whereas gas molecules like nitric oxide (NO) and carbon monoxide (CO) form the class of unconventional neurotransmitters. These molecules are generated spontaneously by way of enzymatic reactions and mediate their biological actions by either activation... 

Table 2 Neurotransmitter Receptor Expression in the Carotid Body...

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