Peripheral chemoreceptors

ExCDDIs certainly improve the efficacy and duration of action of levodopa so that it can be given in a smaller dose (e.g. 25%) and generally in a 4 1 ratio, levodopa ExCDDI. As might be expected, some DA side-effects such as dyskinesia and psychoses are worse, but hypotension is less (no peripheral effects of DA) and vomiting is actually much reduced or abolished. This is because the chemoreceptor trigger zone of the vomiting centre while in the brain is on the blood side of the blood-brain barrier and will not be stimulated since no DA is formed peripherally (Fig. 15.5). That an... 

With most DA agonists there are the other expected signs of increased DA activity such as hallucinations, psychosis and hypotension which can be worse than with levodopa. Fortunately vomiting can be countered by giving the DA antagonist domperidone. This does not cross the blood-brain barrier and so counteracts only the peripheral (chemoreceptor trigger zone) effect of the DA agonist (Fig. 15.5). 

Temporal alterations in peripheral chemoreceptors are rare in vertebrates, but this group provides an example of transient enhancement of signal capture efficiency. The Red-backed salamander (Plethodon cinereus) shows dimorphic and seasonal VNO volume fluctuations. Males always possess a significantly larger vomeronasal area, and both... 

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

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),... 

Compare and contrast the function of the peripheral and central chemoreceptors... 

Carbon monoxide poisoning is particularly insidious. An individual exposed to carbon monoxide is usually unaware of it because this gas is odorless, colorless, and tasteless. Furthermore, it does not elicit any irritant reflexes that result in sneezing, coughing, or feelings of dyspnea (difficulty in breathing). Finally, carbon monoxide does not stimulate ventilation. As will be discussed in a subsequent section, the peripheral chemoreceptors are sensitive to decreases in P02, not oxygen content. 

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. 

A summary of the responses of the peripheral and the central chemoreceptors to reduced arterial oxygen, increased arterial carbon dioxide, and increased arterial hydrogen ion concentration is found in Table 17.2. 

Chemoreceptor response to decreased arterial P02. Hypoxia has a direct depressant effect on central chemoreceptors as well as on the medullary respiratory center. In fact, hypoxia tends to inhibit activity in all regions of the brain. Therefore, the ventilatory response to hypoxemia is elicited only by the peripheral chemoreceptors. 

It is important to note that a decrease in P02 is not the primary factor in the minute-to-minute regulation of ventilation. This is because the peripheral chemoreceptors are not stimulated until the P02 falls to life-threatening levels. A decrease of this magnitude would likely be associated with abnormal conditions, such as pulmonary disease, hypoventilation, or ascent to extreme altitude. 

An increase in arterial PC02 results in marked stimulation of the central chemoreceptors. In fact, this is the most important factor in regulation of ventilation. It is well known that it is impossible to hold one s breath indefinitely. As carbon dioxide accumulates in the arterial blood, the excitatory input to the respiratory center from the central chemoreceptors overrides the voluntary inhibitory input and breathing resumes. Furthermore, this occurs well before the arterial P02 falls low enough to stimulate the peripheral chemoreceptors. 

Chemoreceptor response to increased arterial hydrogen ion concentration. An increase in arterial hydrogen ion concentration, or a decrease in arterial pH, stimulates the peripheral chemoreceptors and enhances ventilation. This response is important in maintaining acid-base balance. For example, under conditions of metabolic acidosis, caused by the accumulation of acids in the blood, the enhanced ventilation eliminates carbon dioxide and thus reduces the concentration of H+ ions in the blood. Metabolic acidosis may occur in patients with uncontrolled diabetes mellitus or when tissues become hypoxic and produce lactic acid. An increase in arterial hydrogen ion concentration has no effect on the central chemoreceptors. Hydrogen ions are unable to cross the blood-brain barrier. 

Beyond this point, during more severe exercise associated with anaerobic metabolism, minute ventilation increases faster than the rate of oxygen consumption, but proportionally to the increase in carbon dioxide production. The mechanism of the ventilatory response to severe exercise involves metabolic acidosis caused by anaerobic metabolism. The lactic acid produced under these conditions liberates an H+ ion that effectively stimulates the peripheral chemoreceptors to increase ventilation. 

Polar substances cannot reach the emetic center itself because it is protected by the blood-brain barriet However, they can indirectly excite the center by activating chemoreceptors in the area postrema or receptors on peripheral vagal nerve endings. 

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. 

The most common peripheral side effects are anorexia, nausea, and vomiting (likely due to dopamine s stimulation of the chemoreceptor trigger zone of the area postrema in the medulla oblongata). 

Mechanism of Action An antiemetic that blocks serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone. Therapeutic Effect Prevents nausea and vomiting. 

Mechanism of Action Aphenothiazinethat acts centrally to inhibit or block dopamine receptors in the chemoreceptor trigger zone and peripherally to block the vagus nerve in the GI tract. Therapeutic Effect Relieves nausea and vomiting and improves psychotic conditions. 

Miscellaneous actions Peripherally formed dopamine (converted peripherally after levodopa therapy) gains access to the CTZ (chemoreceptor trigger zone) causing nausea and vomiting. 

All pure p agonist opioids produce a dose-related depression of ventilation. Pure K agonists have little effect on respiration. The primary effect of opioids is a reduction in the sensitivity of the respiratory centre to C02. They also depress the medullary and peripheral chemoreceptors. Initially, respiratory rate is affected more than tidal volume, which may even increase. With increasing doses respiratory rhythmicity is disturbed resulting in the irregular, gasping breathing characteristic of opioid overdose. The hypoxic drive to ventilation is also depressed by opioids. 

The vagus nerve is a major connection between central and peripheral components. It contains both afferent (80%) and efferent (20%) pathways from and to the upper GIT. These include both cholinergic and non-cholinergic nerve fibres the non-cholinergic neurones may have serotonin as transmitter. Two types of vagal afferent receptors are involved in the emetic response (1) mechanoreceptors, iocated in the muscular wall of the distal stomach and proximal duodenum, which are activated by distension or contraction of the gut wall and (2) chemoreceptors located in the gut mucosa of the upper small bowel. These monitor the... 

When levodopa is given without a peripheral decarboxylase inhibitor, anorexia and nausea and vomiting occur in about 80% of patients. These adverse effects can be minimized by taking the drug in divided doses, with or immediately after meals, and by increasing the total daily dose very slowly antacids taken 30-60 minutes before levodopa may also be beneficial. The vomiting has been attributed to stimulation of the chemoreceptor trigger zone located in the brain stem but outside the blood-brain barrier. Fortunately, tolerance to this emetic effect develops in many patients. Antiemetics such as phenothiazines should be avoided because they reduce the antiparkinsonism effects of levodopa and may exacerbate the disease. 

Most older typical antipsychotic drugs, with the exception of thioridazine, have a strong antiemetic effect. This action is due to dopamine-receptor blockade, both centrally (in the chemoreceptor trigger zone of the medulla) and peripherally (on receptors in the stomach). Some drugs, such as prochlorperazine and benzquinamide, are promoted solely as antiemetics. 

P americana is one of just a few species of insects in which both peripheral and central olfactory processing have been studied. In contrast to many short-lived lepidopterans, in which the male antenna is highly specialized for sex pheromone reception, the antennae of male cockroaches contain numerous food-responsive sensilla. In addition to olfactory sensilla, the antennae also house mechano-, hygro-and thermoreceptors, as well as contact chemoreceptors (Schaller, 1978 review Boeckh et al., 1984). Extensive ultrastructural and electrophysiological evidence has demonstrated that morphologically defined sensillum types house receptor cells of specific functional types (Sass, 1976, 1978, 1983 Schaller, 1978 Selzer, 1981, 1984 review Boeckh and Ernst, 1987). Boeckh and Ernst (1987) defined 25 types of cell according to their odor spectra, but of the 65 500 chemo- and mechanosensory sensilla on the antenna of adult male P. americana, an estimated 37 000 house cells that respond to periplanone-A and periplanone-B. 

Nausea and emesis are common unpleasant side-effects of opioids (Campora et al., 1991 Aparasu et al., 1999). They are most intensively experienced at the beginning of the treatment. During chronic administration, tolerance may occur, which reduces the emetic sequelae. Nausea and emesis are induced via activation of chemoreceptors which are located in the trigger zone of the area postema of the formatio reticularis. The receptors are at the tissue surface and in contact with the circulating blood. Thus the emetic effect of opioids is not mediated centrally, i.e. after penetration of the blood-brain barrier, but rather peripherally via the amount of the compound, which is distributed in the circulating blood. 

Selective 5-HT3 receptor antagonists have potent antiemetic properties that are mediated mainly through peripheral 5-HT3 receptor blockade on intestinal vagal afferents. In addition, central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone probably plays an important role. The antiemetic action of these agents is restricted to emesis attributable to vagal stimulation other emetic stimuli such as motion sickness are poorly controlled. 

Derby, C. D. and Atema, J., Chemoreceptor cells in aquatic invertebrates peripheral filtering mechanisms in decapod crustaceans, Sensory Biology of Aquatic Animals, Atema, J., Fay, R. R., Popper, A. N. and Tavolga, W. N., Eds., Springer-Verlag, New York, 1988, 365. 

Davis E. E. (1984) Regulation of sensitivity in the peripheral chemoreceptor systems for host-seeking behavior by a haemolymph-bome factor in Aedes aegypti. J. Insect. Physiol. 30, 179-183. 

The peripheral sensory neurons that supply the chemoreceptors in the oral cavity reside in four distinct cranial ganglia (Figure 4). The trigeminal ganglion contains the sensory... 

Figure 7. Peripheral innervation of fungiform chemoreceptors by neurons of the...

Although it is common to assert that there are only four distinct taste sensations, even a casual introspection reveals that other oral sensations can be distinguished. As one may expect, flavor chemists have discovered that many separate oral sensations are required to reconstruct the flavors of foods and beverages. Some of these sensations have distinct oral loci from which they are elicited by specified types of chemical compounds, thus indicating that different neural systems are involved. Many of these sensations are difficult to typify verbally and also often have affective overtones. These sensations are the result of considerable peripheral and central neural processing and are only indirectly related to the peripheral neural pulse signals as discussed above. The type of sensation elicited and the locus of elicitation provide us with further measures of the functional properties of oral chemoreceptor systems. 

Lahiri, S. (1996). Peripheral chemoreceptors and their sensory neurons in chronic states of hypo-and hyperoxygenation. Handbk Physiol. 2 1183-1206. 

Q5 Alkalosis can be caused by both metabolic and respiratory problems. Apart from hyperventilation, respiratory alkalosis can be produced by hypoxia, for example, when a person moves to high altitude with a reduced arterial P02, stimulation of respiration occurs via the peripheral chemoreceptors in the carotid and aortic bodies, which respond to the low arterial P02. Increased rate and depth of respiration causes an increased quantity of C02 to be lost from the body, and so pH rises. 

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