Carotid body

Non-neuronal transplants such as adrenal chromaffin cells have been tried but do not survive although some L-dopa-producing cell lines (e.g. PC 12) or glomus cells of the carotid body do produce DA in vivo and may provide the equivalent of a continuous infusion of dopa (and DA) directly into the brain. Expression of tyrosine hydroxylase to promote dopa and DA synthesis in striatal cells by direct gene transfer in vivo or in cultures for subsequent transplanting, may also be possible. (See Dunnett and Bjorklund 1999 for a review of these approaches.)... 

Chemoreceptors. The peripheral chemoreceptors include the carotid bodies, located at the bifurcation of the common carotid arteries, and the aortic bodies, located in the aortic arch. These receptors are stimulated by a decrease in arterial oxygen (hypoxia), an increase in arterial carbon dioxide (hypercapnia),... 

The peripheral chemoreceptors include the carotid and aortic bodies. The carotid bodies, which are more important in humans, are located near the bifurcation of the common carotid arteries. The aortic bodies are located in the arch of the aorta. The peripheral chemoreceptors respond to a decrease in P02/ an increase in PC02, and a decrease in pH (increase in H+ ion concentration) of the arterial blood. 

A2A receptors that are present on sensory nerves in the carotid body, aortic body and elsewhere in the periphery produce excitatory sensory input. These receptors have been implicated in the production of pain associated with angina pectoris, ulcer and the human blister base preparation. 

Results of in vitro studies suggest an interaction between calcium ions and cyanide in cardiovascular effects (Allen and Smith 1985 Robinson et al. 1985a). It has been demonstrated that exposure to cyanide in metabolically depleted ferret papillary muscle eventually results in elevated intracellular calcium levels, but only after a substantial contracture develops (Allen and Smith 1985). The authors proposed that intracellular calcium may precipitate cell damage and arrhythmias. The mechanism by which calcium levels are raised was not determined. Franchini and Krieger (1993) produced selective denervation of the aortic and carotid bifurcation areas, and confirmed the carotid body chemoreceptor origin of cardiovascular, respiratory and certain behavioral responses to cyanide in rats. Bradycardia and hyperventilation induced by cyanide are typical responses evoked by carotid body chemoreceptor stimulation (Franchini and Krieger 1993). 

Franchini KG, Krieger EM. 1993. Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN. J Auton Nerv Syst 42(l) 63-69. 

Carotid body. Sensitivity to arterial pC02 increases increased afferent input augments respiratory rate and depth. 

Chapter 28). Stimulation of nicotinic receptors in adrenergic nerve terminals leads to the release of norepinephrine and activation of nicotinic chemoreceptors in the aortic arch and carotid bodies causes nausea and vomiting. Nicotinic receptors in the central nervous system mediate a complex range of excitatory and inhibitory effects. 

Low doses of nicotine stimulate respiration through activation of chemoreceptors in the aortic arch and carotid bodies, while high doses directly stimulate the respiratory centers. In toxic doses, nicotine depresses respiration by inhibiting the respiratory centers in the brainstem and by a complex action at the receptors at the neuromuscular junction of the respiratory muscles. At these neuromuscular receptors, nicotine appears to occupy the receptors, and the end plate is depolarized. After this, the muscle accommodates and relaxes. These central and peripheral effects paralyze the respiratory muscles. 

Wellhoner et al. 2 reported that intravenous injection of III at 25 mg/kg led to marked hypotension in rats, guinea pigs, rabbits, and cats. The hypotensive effect was particularly marked in old cats that had high blood pressures initially it was not altered by bilateral vagotomy, evisceration, or removal of the carotid bodies, but was reduced or abolished by decapitation. These investigators suggested that the hypotension may result from some effect of the oxime on the CNS. They found also that prior doses of III prevented the hypertensive action of norepinephrine. 

The question as to whether all of the possible iWmethylation compounds of noradrenaline are indeed commonly present in storage places in the body such as the adrenal medulla, or the carotid body, or other ganglia or peripheral synapses will probably not be answered soon, for the intensity of the pharmacological activity of iV -dimethylnoradrenaline and noradrenaline trimethylammonium ion is not great as reported by Stehle, Melville, and Oldham (14) who unfortunately do not give any of the chemical details regarding the identity or purity of the preparations they used. 

Wang ZY, Keith IM, Beckman MJ, Brownfield MS, Vidruk EH, Bisgard GE. 5-HT5A receptors in the carotid body chemoreception pathway of rat. Neurosci Lett 2000 278 9-12. 

Carotid body glomus cell (Signal transduction pathways) -----------7-------- -----------... 

Administration of oxygen-rich gas mixtures is useful in hypoxia, but 100% 02 is not often used. In chronic bronchitis, hypoxia and hypercapnia coexist, the respiratory centre in the medulla becomes tolerant to the high C02 content of blood and is relatively insensitive to it. Respiratory drive is maintained by hypoxia acting via chemoreceptors in the aorta and carotid body. Removal of the hypoxic stimulus to the respiratory centre in the medulla may actually stop the patient breathing. 

Primary sensors are located in the pancreatic islets, and also in the carotid bodies, medulla and the hypothalamus. There are inputs from the eyes, nose, taste buds and gut which signal food is on the way, while fear and stress help prepare the body to face difficult times ahead. 

There are some indications that mammals possess at least two H2O2 sensors. One is located in cells of the lung neuroepithelial bodies, being responsible for constriction of the lung airways when the H2O2 level rises [6,7]. The other performs the same function in the blood vessels, being found in cells of the carotid body [8-10]. 

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. 

Brooker CD, Lawson AD. Convulsions following bupivacaine infiltration for excision of carotid body tumour. Anaesth Intensive Care I993 2I(6) 877-8. 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

Doxapram (respiratory stimulant that activates peripheral aortic and carotid body chemoreceptors) behaves as a physiological antagonist when used to reverse central respiratory depression caused by barbiturates or inhalational anaesthetic agents. 

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