Nicotinic versus Muscarinic Bonding Sites in Cat and Rabbit Carotid Bodies

Hirano, Tomohisa; Dinger, B.; Yoshizaki, Kazuhito; González, C.; Fidone, S.

doi:10.1159/000109319

Cited by 24 publications

(15 citation statements)

References 17 publications

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“…24 -26 This is likely because of the fact that the effects of exogenous nicotine on chemoreceptors depend on the predominance of nicotinic and muscarinic receptors on the carotid bodies. 27 This ratio differs among species, and animal studies on the effects of nicotine on chemoreceptor control are, therefore, difficult to extrapolate to humans. We decided to test the hypothesis that nicotine increases peripheral sympathetic nerve activity to muscle circulation [muscle sympathetic nerve activity (MSNA)] in humans and that it enhances peripheral chemoreflex sensitivity to hypoxia.…”

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confidence: 99%

Acute Cardiovascular and Sympathetic Effects of Nicotine Replacement Therapy

et al. 2006

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Abstract-Sympathetic overactivity is implicated in the increased cardiovascular risk of cigarette smokers. Excitatory nicotinic receptors are present on peripheral chemoreceptor cells. Chemoreceptors located in the carotid and aortic bodies increase ventilation (Ve), blood pressure (BP), heart rate (HR), and sympathetic nerve activity to muscle circulation (MSNA) in response to hypoxia. We tested the hypothesis that nicotine replacement therapy (NRT) increases MSNA and chemoreceptor sensitivity to hypoxia. Sixteen young healthy smokers were included in the study (8 women). After a randomized and blinded sublingual administration of a 4-mg tablet of nicotine or placebo, we measured minute Ve, HR, mean BP, and MSNA during normoxia and 5 minutes of isocapnic hypoxia. Maximal voluntary end-expiratory apneas were performed at baseline and at the end of the fifth minute of hypoxia. Nicotine increased HR by 7Ϯ3 bpm, mean BP by 5Ϯ2 mm Hg, and MSNA by 4Ϯ1 bursts/min, whereas subjects breathed room air (all PϽ0.05). During hypoxia, nicotine also raised HR by 8Ϯ2 bpm, mean BP by 2Ϯ1 mm Hg, and MSNA by 7Ϯ2 bursts/min (all PϽ0.05). Nicotine increased MSNA during the apneas performed in normoxia and hypoxia (PϽ0.05). Nicotine also raised the product of systolic BP and HR, a marker of cardiac oxygen consumption, during normoxia, hypoxia, and the apneas (PϽ0.05). Ve, apnea duration, and O 2 saturation during hypoxia and the apneas remained unaffected. In conclusion, sympathoexcitatory effects of NRT are not because of an increased chemoreflex sensitivity to hypoxia. NRT increases myocardial oxygen consumption in periods of reduced oxygen availability.

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confidence: 99%

Acute Cardiovascular and Sympathetic Effects of Nicotine Replacement Therapy

et al. 2006

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“…In the rabbit, exogenously applied ACh inhibits carotid sinus nerve activity. This response is most likely mediated through the inhibitory muscarinic receptors, where the ratio of muscarinic to nicotinic binding is 12:1, in contrast to a ratio of 1:2 in the adult cat (Hirano et al, 1992). In both species, however, carotid sinus nerve denervation does not alter the amount of muscarinic and nicotinic binding sites in the carotid body, suggesting that nicotinic or muscarinic receptors are not present on afferent nerve endings (Hirano et al, 1992).…”

Section: Cholinergic Neurotransmitter System Involved In Arterial Chementioning

confidence: 89%

“…This response is most likely mediated through the inhibitory muscarinic receptors, where the ratio of muscarinic to nicotinic binding is 12:1, in contrast to a ratio of 1:2 in the adult cat (Hirano et al, 1992). In both species, however, carotid sinus nerve denervation does not alter the amount of muscarinic and nicotinic binding sites in the carotid body, suggesting that nicotinic or muscarinic receptors are not present on afferent nerve endings (Hirano et al, 1992). From the available immunohistochemical studies performed in the rat, ChAT immunoreactivity has been localized to autonomic microganglia in the carotid sinus nerve and in the periphery of the carotid body (Wang et al, 1992), similar to the location of VAChT mRNAs in the carotid body from the same species (Fig.…”

Section: Cholinergic Neurotransmitter System Involved In Arterial Chementioning

confidence: 98%

Gene expression in peripheral arterial chemoreceptors

Gauda

2002

Microscopy Res & Technique

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The peripheral arterial chemoreceptors of the carotid body participate in the ventilatory responses to hypoxia and hypercapnia, the arousal responses to asphyxial apnea, and the acclimatization to high altitude. In response to an excitatory stimuli, glomus cells in the carotid body depolarize, their intracellular calcium levels rise, and neurotransmitters are released from them. Neurotransmitters then bind to autoreceptors on glomus cells and postsynaptic receptors on chemoafferents of the carotid sinus nerve. Binding to inhibitory or excitatory receptors on chemoafferents control the electrical activity of the carotid sinus nerve, which provides the input to respiratory-related brainstem nuclei. We and others have used gene expression in the carotid body as a tool to determine what neurotransmitters mediate the response of peripheral arterial chemoreceptors to excitatory stimuli, specifically hypoxia. Data from physiological studies support the involvement of numerous putative neurotransmitters in hypoxic chemosensitivity. This article reviews how in situ hybridization histochemistry and other cellular localization techniques confirm, refute, or expand what is known about the role of dopamine, norepinephrine, substance P, acetylcholine, adenosine, and ATP in chemotransmission. In spite of some species differences, review of the available data support that 1). dopamine and norepinephrine are synthesized and released from glomus cells in all species and play an inhibitory role in hypoxic chemosensitivity; 2). substance P and acetylcholine are not synthesized in glomus cells of most species but may be made and released from nerve fibers innervating the carotid body in essentially all species; 3). adenosine and ATP are ubiquitous molecules that most likely play an excitatory role in hypoxic chemosensitivity.

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“…The release of ATP from CB was first reported by Buttigieg and Nurse (1) in the rat CB slices in response to intense hypoxic stimulations (15)(16)(17)(18)(19)(20); after that study, our laboratory also described increases in the release of ATP in response to hypoxia (2,6). However, the effect of different hypoxic intensities on ATP CB release was lacking.…”

mentioning

confidence: 93%

“…Very relevant also is the case of ACh, which is the first candidate as the prime neurotransmitter between chemoreceptor cells and the CSN sensory nerve endings (for references see 17). As is the case with dopamine, there are also important species differences in the action of ACh and cholinergic agents on CSN activity (e.g., 27) as well as in the density of nicotinic vs. muscarinic receptors (19). Yet, despite these recognized differences, ACh and nicotinic receptors enjoy the favor of many researchers in the CB field as the main players in the communication between chemoreceptor cells and sensory nerve endings of the CB.…”

mentioning

confidence: 99%

Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensory activity

Conde

Monteiro

Rigual

et al. 2012

Journal of Applied Physiology

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118

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Conde SV, Monteiro EC, Rigual R, Obeso A, Gonzalez C. Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensory activity. J Appl Physiol 112: 2002-2010, 2012. First published April 12, 2012 doi:10.1152/japplphysiol.01617.2011.-Excitatory effects of adenosine and ATP on carotid body (CB) chemoreception have been previously described. Our hypothesis is that both ATP and adenosine are the key neurotransmitters responsible for the hypoxic chemotransmission in the CB sensory synapse, their relative contribution depending on the intensity of hypoxic challenge. To test this hypothesis we measured carotid sinus nerve (CSN) activity in response to moderate and intense hypoxic stimuli (7 and 0% O 2) in the absence and in the presence of adenosine and ATP receptor antagonists. Additionally, we quantified the release of adenosine and ATP in normoxia (21% O 2) and in response to hypoxias of different intensities (10, 5, and 2% O 2) to study the release pathways. We found that ZM241385, an A 2 antagonist, decreased the CSN discharges evoked by 0 and 7% O 2 by 30.8 and 72.5%, respectively. Suramin, a P 2X antagonist, decreased the CSN discharges evoked by 0 and 7% O 2 by 64.3 and 17.1%, respectively. Simultaneous application of both antagonists strongly inhibited CSN discharges elicited by both hypoxic intensities. ATP release by CB increased in parallel to hypoxia intensity while adenosine release increased preferably in response to mild hypoxia. We have also found that the lower the O 2 levels are, the higher is the percentage of adenosine produced from extracellular catabolism of ATP. Our results demonstrate that ATP and adenosine are key neurotransmitters involved in hypoxic CB chemotransduction, with a more relevant contribution of adenosine during mild hypoxia, while vesicular ATP release constitutes the preferential origin of extracellular adenosine in high-intensity hypoxia.adenosine; hypoxia; carotid body CAROTID BODIES (CB) are major peripheral chemoreceptor organs that release neurotransmitters in response to hypoxia, generating action potentials at the carotid sinus nerve (CSN) that are integrated in the brain stem to induce a hyperventilatory compensatory response (17). Among the neurotransmitters released in the CB are adenosine and ATP (1-3). One of the first studies on the effects of ATP on CSN activity was carried out by McQueen and Ribeiro (24) where they showed in vivo in the cat CB that ATP increased CSN activity in a dosedependent manner. Additional experiments led them to conclude that the excitatory action of ATP was due to the adenosine formed by its extracellular degradation. More recently, Zhang and co-workers (47) showed that the coapplication of blockers of nicotinic and P2X receptors, hexamethonium and suramin, respectively, in cocultures of glomus cells and "juxtaposed" petrosal ganglions completely abolished the hypoxiaevoked excitatory postsynaptic responses. They concluded that ATP and ACh, acting as cotransmitters, supported the s...

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Nicotinic versus Muscarinic Bonding Sites in Cat and Rabbit Carotid Bodies

Cited by 24 publications

References 17 publications

Acute Cardiovascular and Sympathetic Effects of Nicotine Replacement Therapy

Acute Cardiovascular and Sympathetic Effects of Nicotine Replacement Therapy

Gene expression in peripheral arterial chemoreceptors

Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensory activity

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