Mechanisms Of Chemoreception Research Articles

Hyperosmolality alters the ventilatory response to acute hypercapnia and hypoxia

Acute hyperosmolality in the Pekin duck results in an extracellular acidosis and hypercarbia without any stimulation of ventilation. The development of the extracellular acidosis is accompanied by the concurrent development of an intracellular alkalosis systematically which has been hypothesized to depress ventilation (Kasserra et al., J. Appl. Physiol., 1993). In order to investigate this apparent suppression of ventilation, the ventilatory response to various respiratory challenges (CO 2, O 2, K +) was studied both before (normosmotic) and after (hyperosmotic) hypertonic sucrose infusion. Increased plasma osmolality caused a significant drop in arterial pH of 0.06 ± 0.01 units and a 4 Torr increase in Pa CO 2 , yet did not stimulate any significant increase in ventilation despite a significant increase in oxygen consumption. Acute hyperosmolality increased the Pa CO 2 associated with resting ventilation, and decreased the magnitude of the ventilatory response to a given increase in Pa CO 2 , compared with the response to the same ventilatory challenge in normosmotic animals. Acute hyperosmolality increased the ventilatory response to hypoxia and K + compared with normosmotic animals. The opposite effect of hyperosmolality on the ventilatory responses to hypercapnia compared with hypoxia suggests that the mechanisms of chemoreception for hypercapnia and hypoxia are different. The depressed ventilatory response curve to increased Pa CO 2 and decreased arterial pH during hyperosmolality, both alone and during the hypercapnic challenge, suggests that the peripheral chemoreceptor response to pH and CO 2 is suppressed. It is hypothesized that the suppression results from the intracellular alkalosis occurring during acute hyperosmolality.

Hyperbaric oxygenation alters carotid body ultrastructure and function

We previously demonstrated that chronic normobaric hyperoxia (NH) for 60–67 h attenuated the carotid chemosensory response to hypoxia, probably initiated by the generation of reactive oxygen species (ROS). Since biological systems are affected by oxygen in a dose-dependent manner, we hypothesized that hyperbaric oxygenation (HBO) would affect the cellular mechanisms of oxygen chemoreception in a shorter time. To test the hypothesis, we studied the effects of oxygen at 5 atmosphere absolute (ATA) on cats ( n = 7) carotid body ultrastructure and chemosensory responses to hypoxia, hypercapnia, and to bolus injections of cyanide, nicotine and dopamine. Four control cats breathed room air at 1 ATA. At the termination of the experiments, carotid bodies from 4 cats in each group were fixed and prepared for electron microscopy and morphometry. On the average, HBO diminished the chemosensory responsiveness to hypoxia ( P<0.01, unpaired t-test) within about 2 h, supporting the hypothesis. The responses to hypercapnia or bolus injections of cyanide, nicotine and dopamine were normal. HBO did not diminish the distribution of the densecored vesicles but significantly increased the mean volume-density of mitochondria and decreased the cristated areap per mitochondrion in the glomus cells. The latter suggests a link between oxidative metabolism and chemosensing, and the former excludes availability of neurotransmitters being the cause of the blunted chemosensory response to hypoxia.

Optical measurements of microvascular oxygen pressure and intracellular pH in the cat carotid body: testing hypotheses of oxygen chemoreception.

The mechanism(s) of oxygen chemoreception by the carotid body is not understood. One current hypothesis states that hypoxic chemoreception is mediated by acid formation in the chemoreceptor cells (Hanson et al., 1981, Eyzaguirre et al, 1983, Fidone and Gonzalez, 1986). Using exogenously supplied lumiphors and video imaging methodology, we tested this hypothesis by monitoring changes in microvascular oxygen pressure and intracellular pH with those of chemosensory activity during oxygen deprivation. These studies were conducted using an in vitro preparation of the cat carotid body that was perfused and superfused with cell-free Tyrode solution (Iturriaga et al, 1990).

Optical measurements of oxygen and electrical measurements of oxygen chemoreception in the cat carotid body.

Measurements of oxygen pressures within the carotid body have been of particular importance for elucidating the mechanism(s) of oxygen chemoreception. An optical technique based on the quenching of phosphorescence by oxygen that is capable of imaging oxygen within the microvasculature has been developed (Rumsey et al, 1988, Wilson et al, 1991). These optical measurements are non-invasive and in particular have the advantage of determining oxygen pressures throughout the entire tissue. We have previously applied this technology to the study of the isolated perfused/superfused cat carotid body and oxygen chemoreception (Rumsey et al, 1991), relying primarily on imaging of phosphorescence intensity. Although the latter is quite useful for following dynamic changes in oxygen pressures, calculation of oxygen pressure is only qualitative. In addition, the carotid body was perfused and superfuised with cell-free media (Iturriaga et al, 1991). In the present report, we describe measurements of oxygen pressure determined from images in phosphorescence lifetimes (Wilson et al, 1991) in the cat carotid body using an in vivo preparation (Lahiri and DeLaney, 1975). These determinations were compared to those obtained previously with the in vitro preparation, thereby permitting comparison of the oxygenation of this organ in the presence and absence of blood, respectively. In both cases, chemosensory discharge was recorded in order to provide measurements of the expression of oxygen chemoreception.

A Cardiogenic Hypertensive Chemoreflex

A cardiogenic hypertensive chemoreflex is elicited by serotonin administered experimentally in the dog. The reflex nearly doubles aortic pressure within 4-6 sec and is associated with powerful inotropic, chronotropic, and dromotropic responses. The afferent pathway is via intrathoracic vagal branches, whereas the efferent paths engage not only the vagal and sympathetic routes but also the phrenic nerve. The reflex can be abolished by vagotomy or with cyproheptadine, and can be attenuated by local anesthesia of the intertruncal space. Small chemoreceptors lying between the aorta and pulmonary artery are the source of the reflex, and they receive their blood supply from the proximal left coronary artery. Human counterparts of the reflex may include new hypertension during angina pectoris or acute myocardial infarction, new postoperative hypertension after coronary bypass grafting, and hypertensive patients with carcinoid syndrome. Many unresolved problems include the precise mechanism of chemoreception, whether the chemoreflex has any tonic influence, and mechanisms of integration of the reflex with other events peripherally and centrally. Answers to these questions could be of great clinical value.

Catecholamines in the carotid body are unaffected by hypercapnia

In contrast to the increased content of dopamine and norepinephrine in rat carotid body during hypoxia (10% O 2 in nitrogen) for 3 and 21 days, hypercapnia (8% CO 2 in air) for 21 days failed to alter the catecholamine concentrations. DOPAC content was elevated in hypoxia whereas there were no significant changes in hypercapnia. This finding supports the view that the mechanisms of peripheral chemoreception differ, at least partly, in hypoxia and hypercapnia.

Diethyl pyrocarbonate (an imidazole binding substance) inhibits rostral VLM CO2 sensitivity

Diethyl pyrocarbonate (DEPC) has been useful in vitro as an agent relatively specific for binding to imidazole of histidine. Administered via the cisterna magna DEPC inhibits central chemosensitivity in conscious rabbits, supporting the alphastat hypothesis for central chemoreceptor function. In this study I have applied DEPC via 1 X 3 mm cottonoid pledgets to each of the three ventrolateral medulla (VLM) chemosensitive areas in glomectomized, vagotomized, paralyzed, and servo-ventilated alpha-chloralose-urethan-anesthetized cats. CO2 responses measured by integrated phrenic nerve output were evaluated before and after DEPC application. A dose of 40 mmol/l applied to the rostral chemosensitive area increased the CO2 threshold (5.3%) and significantly decreased (P less than 0.03; Wilcoxon sign rank test) the initial slope (-43%) and the maximum (-41%) of the CO2 response. No significant effects were observed with DEPC application in the intermediate or caudal areas. Treatment with 40 mmol/l hydroxylamine immediately after DEPC in the rostral area prevented the effects supporting the interpretation that imidazole was the reactant with DEPC. The results are consistent with the hypothesis that imidazole-histidine is involved in the mechanism of central chemoreception and indicate that only the rostral area utilizes a DEPC inhibitable mechanism.

Structure/activity relationships in sweetness

Although several classes of chemical compound may elicit a sweet response, the quality of sweetness appears to be dependent on molecular structure and, in particular, the temporal characteristics of the response bear a relationship to chemical class. Most of the recent chemical research on sweetness has centred on stereochemistry of the stimulus molecule but it is likely that the solution properties and thermodynamic behaviour of the molecule also play a part in the sweet response and must be considered as a clue to the mechanism of taste chemoreception. Intensity/time relationships in sweetness may be partly interpretable in terms of the kinetics of hydration of sweet molecules and the disturbance of water structure. This approach leads to an explanation of molecular accession to receptors and the sensory perception of binary mixtures.

Metabolic regulation of aortic chemoreceptor responses to CO 2

Modification of the usually feeble responses of aortic chemoreceptors to CO 2 was studied in cats which were anethetized, paralyzed, artificially ventilated and maintained at 38°C. The inhibitor of oxidative phosphorylation, oligomycin, strikingly augmented the initial responses to CO 2 of aortic chemoreceptors just as for carotid chemoreceptors, indicating that the basic mechanism of chemoreception might be regulated in part through energy metabolism.

Discontinuous Change in Membrane Activities of Plasmodium of &lt;I&gt;Physarum polycephalum&lt;/I&gt; Caused by Temperature Variation: Effects on Chemoreception and Ameboid Motility

Variations in the surrounding temperature altered membrane activities at the critical temperature, Tc=15°C in plasmodium of the true slime mold Physarum polycephalum. Changes in the membrane and zeta potentials, which were induced by chemical stimuli, decreased when the temperature decreased below Tc. The adsorption energy of a -CH2- group on the membrane changed discretely by about 100 cal/mol at Tc. Decreasing the temperature sharply diminished the extension of psuedopodia by a factor of 1/10 at TC, while the motive force of protoplasmic streaming remained con-stant. This suggests that the formation of pseudopodia and the generation of motive force are different functions in ameboid motility. Results indicate that the surface membrane of the plasmodium undergoes a conformational change at Tc. The mechanisms of chemoreception and motility in plasmodium are discussed.

Potencies of combined doses of nucleotides as gorging stimulants for Rhodnius prolixus

The four nucleotides ATP, UTP, deoxyATP, and A(TETRA)P (adenosine tetraphosphate) were tested singly and in combinations for their potency in eliciting the gorging response of Rhodnius prolixus. All mixtures of ATP and dATP, and ATP and UTP, were more potent by a factor of 1.25 to 1.9 than predicted from their potencies when tested singly. No significant synergism or inhibition was seen with combinations of UTP and dATP, or ATP and A(TETRA)P. Lack of competitive inhibition suggests that physical fit between stimulating molecule and chemoreceptive protein rather than enzymatic modification of the stimulant is the mechanism of chemoreception of these compounds. The slight synergism seen is explained by competitive inhibition of a salivary ATPase.

A theoretical investigation of radiation mechanisms of insect chemoreception

A theoretical investigation is performed of the hypothesis that certain insect sensory receptors operate by modal radiation mechanisms, i. e. as dielectric waveguide or resonator aerials, at infrared wavelengths, in the process of chemoreception and temperature measure­ment. The basic physical principles, requirements, and limitations of such mechanisms are discussed. The criterion chosen for the detectability of radiation emitted (absorbed) by stimulus molecules is that the increment (decrement) in signal power be greater than that from fluctua­tions in the background power from sky and ground. Thermal equilibrium processes . Mechanisms involving the emission of characteristic wave­lengths of radiation by vibrationally or rotationally excited odorant molecules in thermal equilibrium with their surroundings, or involving the absorption of characteristic wavelengths of background radiation by odorant molecules in the ground state, are analysed. For both emission and absorption mechanisms, required concentrations of odorant molecules are much greater than observed sensitivity thresholds for pheromones and most scents. There are also severe limitations on the discriminatory ability of any singly innervated sensillum. Non-equilibrium processes . Detection of stimulated or spontaneous emission of infrared radiation from low concentrations of odorant molecules released in excited states by a living organism is extremely difficult. Even for wavelengths in the 3 to 4μm atmospheric window the advantages of non-equilibrium processes are cancelled by the effects of collisions and other factors. However, radiation from fires is readily detectable, by day or night, in the 3 to 4μm window. Triggering of acceptors by non-radiative processes, in which specificity is determined principally by infrared spectrum, is theoretically possible and merits further investigation. Thus radiation mechanisms cannot provide a general mechanism of chemoreception, and in particular cannot account for pheromone detection, but might only operate in rare special cases, for which critical experiments are proposed. A theoretical model of operation of the honeybee pit-organs as dielectric resonators has been constructed as an illustrative example for the analysis.

Mitochondrial respiratory chain of carotid body and chemoreceptor response to changes in oxygen tension.

Mitochondrial respiratory chain of carotid body and chemoreceptor response to changes in oxygen tension.

Naphthoquinone inhibitors of Periplaneta americana and Scolytus multistriatus feeding: Ultraviolet difference spectra of reactions of juglone, menadione, and 1,4-naphthoquinone with amino acids and the indicated mechanism of feeding inhibition

The relative reactivity of 3 naphthoquinones, which are feeding inhibitors for Periplaneta americana and Scolytus multistriatus, with each of 7 amino acids was measured by ultraviolet difference spectroscopy. Juglone (5-hydroxy-1,4-naphthoquinone), menadione(2-methyl-1,4-naphthoquinone) or 1,4-naphthoquinone produced difference spectra immediately upon mixing with cysteine, but not with valine, serine, glutamic acid, arginine, tryptophan or proline in phosphate buffer (pH 7.0). The K s values for the reactions indicated that the affinities of 1,4-naphthoquinone ( K s = 4.4 · 10 −4 M) and juglone ( K s = 8.3 · 10 −4 M) for cysteine were comparable, but were both approx. 10 times greater than that for menadione ( K s = 3.2 · 10 −3 M). The extinction coefficient of the complex formed by cysteine with juglone ( A = 3.448 · 10 −1 M) was approx. 2 times greater than that of 1,4-naphthoquinone ( A = 1.290 · 10 −1 M) or menadione ( A = 1.176 · 10 −1 M). The importance of these results to explaining the mechanism of chemoreception in P. americana and S. multistriatus is discussed.

Investigation of the mechanism of chemoreception

A study was made of the effect produced by TEA on the reception of ACh, nicotine, and acids. As established, TEA blocked the reception of nicotine by the receptors, did not affect the action of acids, and only partially depressed the ACh reception; the part of the reaction in response to ACh which remained after the TEA action was blocked in this case with ATP. A conclusion was drawn that in effecting the reaction of the given area to ACh considerable significance is played both by this direct action upon the receptors and by their mechanical stimulation as a result of musculature spasm; it also followed that the ACh transmission in this area was absent.

Investigation of the mechanism of chemoreception

The author investigated the effect of different concentrations of monoiodacetic acid (MIA) on the reception of nicotine and acids. It was shown that during the action of MIA in weak concentration (0.0005 M) the excitability in response to both stimuli augments at first and then becomes irreversibly disturbed; the action of nicotine changes but insignificantly. Higher MIA concentrations disturb the nicotine reception as well, however, this effect is reversible. A conclusion is drawn on the existence of separate reactive systems— for nicotine and for acids, with different metabolism.

Role of tricarboxylic acid cycle in mechanisms of chemoreception

Short-term experiments were performed on cats. The isolated intestine, retaining connections with the organism, was perfused with various substances. The glycolysis inhibitor (sodium fluoride) and inhibitor of the tricarboxylic acid cycle (hydroxylamine) depress the intestinal sensitivity to acetylcholine. Addition of the final product of glycolysis to the perfusate (pyruvic or lactic acid) accelerates the restoration of intestinal receptor sensitivity disturbed by sodium fluoride; however, it does not aid in restoration of the intestinal receptor sensitivity disturbed by hydroxylamine. The data presented above lead to the conclusion that not only inhibitors of glycolysis, but also of the tricarboxylic acid cycle belong to the group of substances inhibiting chemoreception. Consequently, all the links of tissue-energy metabolism are connected with the intestinal chemoreception.

The mechanisms of chemoreception

The author has established a direct, but not proportional relationship between the concentration of acetylcholine and the intensity of the reflexes from cholinergic receptors expressed by the formula: $$H_2 = H_1 .2^{lg} \frac{{C_2 }}{{C_1 }}$$ where C1 is the first and C2—the second concentration of acetylcholine; H1—the value of the reflex in response to C2 and H2—in response to C2.

Electrophysiologic investigation of the mechanism of chemoreception

Electrophysiologic investigation of the mechanism of chemoreception

Electrophysiological investigation of the mechanism of chemoreception

The reception of various groups of chemical stimuli (nicotine and certain acids) was studied in conditions of deranged metabolism of intestinal tissue under the influence of various doses of monoiodoacetic acid. Experiments were performed with perfusion of an isolated portion of intestine connected to the organism by nerves alone. As the effect of monoiodoacetic acid becomes more pronounced the increase of the afferent impulse flow ceases and reflex changes of the blood pressure disappear. Reactions of nicotine are re-established, the afferent flow increase and the reflex changes of the blood pressure recur after washing in Ringer-Locke's solution. At the same time, administration of acid depresses the impulse flow and causes depressive reactions of the blood pressure. The conclusion was reached that the mechanisms blocked by monoiodoacetic acid evidently take no part in reception of nicotine and drugs with a similar effect. The reception of acids is impossible after specific block of these mechanisms.