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PubMed1977

APUD cells and the apudomas. A concept relevant to anaesthesia and endocrinology.

A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described.

APUD Cells↗
PubMed1993

[Localization of penicillin G chemoreceptors in cells of Streptomyces sp. R61].

The purpose of the present work was localization of penicillin-binding proteins (PBPs) in the cells of Streptomyces sp. R61 using immunological and autoradiographic methods and electron microscopy. The cells were treated with H3-penicillin G. PBPs of protoplasts were marked with peroxidase labelled IgG to DD-carboxypeptidase of the strain. The results indicate areas privileged in PBPs content at the cytoplasmic membrane and in vesicles located in the periplasmic space. PBPs were visualized in bulges of the protoplasts membrane. In the cells PBPs are present at hyphal tips and in centers at the periphery of cells, which are places of cross wall biosynthesis or branching of hyphae and overproduction of cell wall material.

Binding Sites↗
PubMed1991

Chemosensory responses to mixtures: a model based on composition of receptor cell types.

Previous mixture models have assumed that members of a population of chemoreceptor cells are homogeneous in type, i.e., with either single shared or multiple independent receptor sites. In reality, many chemosensory systems actually consist of a heterogeneous population of receptor cells, consisting of both highly specific cells as well as more broadly and variably tuned cells. A mixed receptor composition model for binary mixtures is described which can be applied to chemosensory systems with heterogeneous receptor cell compositions. The model incorporates information on a) the number of receptor sites/transduction processes per cell, b) the specificity of receptor cells, and c) the contribution of the magnitude of response of each receptor cell to the overall response magnitude of the population of all receptor cells. The predictions of this model can be compared to behavioral responses of animals towards binary mixtures, or at any level of sensory processing which involves the input of the receptor cell population, in order to detect possible mixture interactions.

Animals↗
PubMed1998

Oxygen-sensing mechanisms are present in the chromaffin cells of the sheep adrenal medulla before birth.

1. The ability of the fetal adrenal medulla to respond directly to hypoxaemia and secrete catecholamines before the development of a functional innervation of the gland is essential for intrauterine survival. The cellular mechanisms involved in this response to low PO2 are not known, although the presence of oxygen-sensitive K+ channels in carotid body chemoreceptor cells and other sites suggests that these might underlie the chromaffin cell response. 2. Whole-cell patch-clamp techniques have been used to study K+ currents during normoxia and hypoxia in chromaffin cells isolated from the adrenal glands of fetal sheep. 3. Two types of chromaffin cells were observed, those with a fast inactivating K+ current and a larger capacitance and those with a delayed K+ current and smaller capacitance. No cell showed both types of current. The fast inactivating current showed voltage-dependent inactivation and was blocked by 1 mM 4-aminopyridine, characteristics of an IA-type current. The delayed current had two components, a TEA-sensitive, Ca2+-dependent current and a component with the kinetic behaviour of a delayed rectifier. 4. Both types of current were oxygen sensitive. The IA-type current was reduced by 27.4 +/- 3.2 % when the PO2 was reduced to about 15 mmHg. With the delayed current, hypoxia reduced the amplitude by 26.9 +/- 2.4 %, largely by reduction of the Ca2+-dependent component. 5. In the presence of hypoxia, reduction in the amplitude of these oxygen-sensitive K+ currents would increase the frequency and duration of action potentials, leading to increased activation of the L-type Ca2+ channels, influx of Ca2+ and the subsequent secretion of catecholamines.

Adrenal Glands↗
PubMed2002

Carotid body chemoreceptors in dissociated cell culture.

Carotid body (CB) glomus or type 1 cells act as peripheral chemoreceptors which detect changes in arterial PO(2), PCO(2), and pH and help maintain homeostasis via the reflex control of ventilation. Over the last approximately 12 years significant progress has been made towards understanding chemotransduction mechanisms using freshly isolated or cultured type 1 cells. The latter preparation allows several powerful experimental manipulations (e.g., co-culture with sensory neurons) resulting in significant advances in our understanding of CB chemoreception. Here, we review several properties of type 1 cells after several days to weeks in culture. Typically, cultured type 1 cells grow in monolayer clusters enveloped by glial-like, type II, or sustentacular cells, which are immunopositive for the glial marker, glial fibrillary acid protein (GFAP). These cells can undergo DNA synthesis, evidenced by uptake of bromodeoxyuridine (BrdU), and show a limited capacity for cell division. Mitosis and survival of type 1 cells can be regulated by oxygen tension and/or growth factors (e.g., bFGF, insulin). In the rat, type 1 cells are immunopositive for several monoaminergic markers, including tyrosine hydroxylase (TH), dopamine transporter (DAT), and 5-HT. They also express cholinergic markers (e.g., vesicular acetylcholine transporter; VAChT), the highly conserved synaptic vesicle protein (SV2), and gap junctional proteins including Connexin 32 (Cx32). Moreover, in long-term culture ( approximately 2 weeks) they retain expression of O(2)-sensitive, TASK-1-like, and Ca(2+)-dependent (BK), K(+) channels as revealed by immunocytochemistry or RT-PCR analysis of mRNA extracted from type 1 clusters after removal from the culture surface.

Animals↗
PubMed1990

So-called minute chemodectoma of the lung. An electron microscopic and immunohistochemical study.

So-called minute pulmonary chemodectoma is a curious, small lung tumour found mainly in women. The nature and origin of the proliferating cells are still obscure. In the first report on the tumour, the component cells were described as resembling chemoreceptor cells and the tumour was named chemodectoma. However, electron microscopic studies of the tumour have revealed no evidence of neuronal characteristics and have shown a close resemblance to meningothelial cells. In this study, the electron microscopic findings were similar to those previously reported but in one of the two cases, tumour cells were filled with abundant cytofilaments, giving them an occasional dense, patch-like appearance. Immunostaining for myosin and vimentin was positive in all tumour cells, but epithelial membrane antigen staining was not seen. These findings indicate that the tumour might have its origin from muscle cells.

Aged↗
PubMed1999

Cells of the carotid body express connexin43 which is up-regulated by cAMP.

We identified a gap junction protein subunit, connexin43 (Cx43) by immunofluorescence and immunoblotting, in cultured rat carotid body cells and in whole organs. In 1-week-old cultures, all cells were flat but after 3 h exposure to 8Br-cAMP (1 mM), tyrosine hydroxylase (TH) positive cells (chemoreceptors), but not TH negative cells, adopted a round body with multiple thin arborization processes. The incidence of dye coupling between cultured cells of the same type increased from 26% in controls to 73% after treatment with 8Br-cAMP. In control cultures, Cx43 immunoreactivity showed a diffuse perinuclear distribution and after 8Br-cAMP treatment, it was also found at cell-cell contacts. Both 8Br-cAMP-induced dye coupling and cellular redistribution of Cx43 were blocked by pretreatment with actinomycin D (5 microM), a mRNA transcription blocker. Moreover, 3 h exposure to 8Br-cAMP increased the levels of Cx43 in entire organs. We suggest that conditions that promote a sustained increase in cytosolic cAMP up-regulate coupling between carotid body cells in a transcription-dependent manner. The possible functional significance of these findings is discussed.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells.

Fluoxetine, an antidepressant which is used world-wide, is a prominent member of the class of selective serotonin re-uptake inhibitors. Recently, inhibition of voltage-gated Na(+) and K(+) channels by fluoxetine has also been reported. We examined the effect of fluoxetine on voltage-gated calcium channels using the patch-clamp technique in the whole-cell configuration. In hippocampal pyramidal cells, fluoxetine inhibited the low-voltage-activated (T-type) calcium current with an IC(50) of 6.8 microM. Fluoxetine decreased the high-voltage-activated (HVA) calcium current with an IC(50) between 1 and 2 microM. Nifedipine and omega-conotoxin GVIA inhibited the HVA current by 24% and 43%, respectively. Fluoxetine (3 microM), applied in addition to nifedipine or omega-conotoxin, further reduced the current. When fluoxetine (3 microM) was applied first neither nifedipine nor omega-conotoxin attenuated the remaining component of the HVA current. This observation indicates that fluoxetine inhibits both L- and N-type currents. In addition, fluoxetine inhibited the HVA calcium current in carotid body type I chemoreceptor cells and pyramidal neurons prepared from prefrontal cortex. In hippocampal pyramidal cells high K(+)-induced seizure-like activity was inhibited by 1 microM fluoxetine; the mean burst duration was shortened by an average of 44%. These results provide evidence for inhibition of T-, N- and L-type voltage-gated calcium channels by fluoxetine at therapeutically relevant concentrations.

Action Potentials↗
PubMed2004

Intrinsic nitric oxide regulates the taste response of the sugar receptor cell in the blowfly, Phormia regina.

The taste organ in insects is a hair-shaped taste sensory unit having four functionally differentiated contact chemoreceptor cells. In the blowfly, Phormia regina, cGMP has been suggested to be a second messenger for the sugar receptor cell. Generally, cGMP is produced by membranous or soluble guanylyl cyclase (sGC), which can be activated by nitric oxide (NO). In the present paper, we electrophysiologically showed that an NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO), an NO donor, 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC 7) or an NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) specifically affected the response in the sugar receptor cell, but not in other receptor cells. PTIO, when introduced into the receptor cells in a sensillum aided by sodium deoxycholate (DOC, pH 7.2), depressed the response of sugar receptor cells to sucrose but did not affect those of the salt or water receptor cells. NOC 7, given extracellularly, latently induced the response of sugar receptor cells; and L-NAME, when introduced into the receptor cells, depressed the response of sugar receptor cells. The results clearly suggest that NO, which may be produced by intrinsic NOS in sugar receptor cells, participates in the transduction cascade of these cells in blowfly.

Animals↗
PubMed1959

Electron microscopic observations of the carotid body of the cat.

Carotid bodies were removed from cats, fixed in buffered 1 per cent osmic acid, embedded in deaerated, nitrogenated methacrylate, and cut into thin sections for electron microscopic study. The carotid body is seen to be composed of islands of chemoreceptor and sustentacular cells surrounded by wide irregular sinusoids. These cells are separated from the sinusoids by relatively broad interstitial spaces which are filled with collagen, fibroblasts, and many unmyelinated nerve fibers with their Schwann cell sheaths. The chemoreceptor cells are surrounded by the flattened, multiprocessed sustentacular cells which serve to convey the axons from an interstitial to a pericellular location. These sustentacular cells are assumed to be lemmoblastic in origin. Relatively few axons are seen to abut on the chemoreceptor cells. The cytoplasm of the chemoreceptor cell is characterized by numerous small mitochondria, units of granular endoplasmic reticulum, a small Golgi complex, and a variety of vesicles. There are many small vesicles diffusely scattered throughout the cytoplasm. In addition, there is a small number of dark-cored vesicles of the type which has been previously described in the adrenal medulla. These are usually associated with the Golgi complex. These findings are discussed in relation to the concepts of the origin of the chemoreceptor cell and the nature of the synapse.

Adrenal Medulla↗
PubMed1990

Peripheral mechanisms of olfactory discrimination of complex mixtures by the spiny lobster: no cell types for mixtures but different contributions of the cells to the across neuron patterns.

Toward understanding mechanisms of olfactory discrimination, we have examined the existence of cell types and the role of cells in the coding of odorant quality in the olfactory organ of the spiny lobster. The results consisted of responses of 30 antennular chemoreceptor cells to 8 behaviorally discriminable complex stimuli--4 natural extracts and 4 artificial mixtures, each at 3 concentrations. Multidimensional scaling and cluster analysis failed to identify unequivocal cell types, but rather suggested a continuum of cellular response profiles. The lack of cell types suggests that the code for the quality of natural odorants in this system is a population code. The distribution of cells along the response continuum was based on any of many features of their response profiles. The most effective stimulus (= best stimulus) and the least effective stimulus (= least stimulus), two features of the response profiles, could only partially explain the differences in response profiles of cells. Nonetheless, cells with different response profiles were shown to have different functions in odorant coding. Most cells contribute to some degree to the discrimination of any two stimuli, but a cell's contribution to the discrimination of two stimuli is usually disproportionally robust when those two stimuli produce very different responses in that cell.

Action Potentials↗
PubMed1987

Eukaryotic unicells: how useful in studying chemoreception?

The description of the chemoreception pathway in Paramecium is incomplete, but the technical means are available to study these pathways at the molecular level. The hallmark of ciliates is their versatility and their most important attribute is the availability of useful mutants. It is just this versatility and amenability to genetic manipulation that will move the study of Paramecium chemoreception forward and provide useful information for chemoreceptor cell function in general.

Animals↗
PubMed1970

The effects of amino acids on the labellar hair chemosensory cells of the fly.

The effects of amino acids on the labellar hair chemosensory cells were examined with two kinds of flies (the fleshfly, Boettcherisca peregrina, and the blowfly, Phormia regina). As a result of this examination, the effects of amino acids were divided into four main classes. Amino acids in class 1 did not stimulate any chemoreceptor cell. Amino acids in class 2 inhibited nonspecifically the discharges from three kinds of chemosensory cells. Amino acids in class 3 stimulated the salt receptor cell. Amino acids in class 4 stimulated the sugar receptor cell. A possibility that a fourth neuron in the labellar hair chemosensory cell might be a protein or an amino acid receptor cell was eliminated.

Amino Acids↗
PubMed2005

Retrotrapezoid nucleus: a litmus test for the identification of central chemoreceptors.

Central chemoreception is the mechanism by which arterial blood P(CO2) is detected by the CNS to regulate breathing. Two main theories have been proposed to account for the phenomenon. The distributed chemosensitivity theory argues that pH sensitivity is a widespread attribute of brainstem neurones and that central chemoreception results from the cumulative effects of pH on countless neurones. The specialized chemoreceptor theory envisions the existence of small and specialized populations of CNS cells (chemoreceptors) that are unique in their ability to detect very small pH fluctuations and, via specific connections, regulate a respiratory network that is itself unresponsive to pH. The recently identified CO2-sensitive neurones of the retrotrapezoid nucleus (RTN) seem to possess most of the attributes that one would expect of such chemoreceptors. In this review we also suggest that many fewer medullary neurones are intrinsically responsive to CO2 in vivo than might have been anticipated from prior experimentation in vitro. The properties of RTN neurones provide renewed support for the specialized chemoreceptor theory of central chemoreception, proposed in the early 1960s. However, many uncertainties remain, especially as regards the molecular mechanisms of chemoreception, the type of cell that actually detects pH in vivo (neurone, glia or others) and the number and location of bona fide central chemoreceptors.

Afferent Pathways↗
PubMed1998

Replacement of receptor cells in the hamster vomeronasal epithelium after nerve transection.

Chemoreceptor cells in the vomeronasal and olfactory epithelium are replaced following experimentally induced degeneration. This study analyzes quantitatively the time course and degree of vomeronasal receptor cell replacement. Unilateral transection of the vomeronasal nerves in adult hamster was used to induce a retrograde degeneration of receptor cells in the vomeronasal organ. Histological measurement of both number of receptor cells and epithelial thickness were made for recovery times from 0 to 60 days. After nerve transection, there was a gradual degeneration of receptor cells, the number decreasing to 50% of control by day 2 and 16% by day 6. During days 7-15 maximum receptor cell replacement was observed. Cell number increased rapidly and reached a peak on day 15. At recovery times of 40-60 days, cell number returned to the control level. Epithelial thickness, however, decreased to 60-70% during the degeneration period (days 4-6) and did not return to control levels. After 40-60 days epithelial thickness remained at 70% of control. These results demonstrate that vomeronasal receptor cells are replaced following degeneration, but epithelial thickness does not return to control levels. These findings suggest that the number of replacement cells is not limited by the reduced thickness of the epithelium, and that recovery mechanisms may function to restore an optimum number of receptor cells.

Animals↗
PubMed1993

Distribution of calcium binding proteins in sensory organs of the ear, nose and throat.

Distributions of spot-35 protein (S-35), calbindin (CaB), and parvalbumin (PaV), three types of calcium-binding protein, were examined immunohistochemically in sensory organs of the ear, nose and throat in guinea pigs and rats. Immunoreactivity of S-35 and CaB was found in the outer hair cells and in vestibular sensory cells situated at the top of the ampulla, and in some cells in the macula. Microvillar cells in the olfactory epithelium, periglomerular cells, and small numbers of cells in the mitral cell layer in the olfactory bulb reacted to anti-S-35 and anti-CaB antisera. In taste buds, most gustatory receptor cells reacted to anti-CaB, although a few reacted to anti-S-35 antiserum. Neuron-like cells in the upper respiratory tract reacted similarly to these antisera. No PaV-immunoreactivity was found in any region. These results indicate that S-35 and CaB play important roles in the special kinds of mechanoreceptor and chemoreceptor cells found in the otolaryngeal area.

Animals↗
PubMed1991

Quantitative studies of the vasculature of the carotid body in fetal and newborn sheep.

Resetting of the hypoxic sensitivity of the carotid chemoreceptors from the fetal to the adult arterial PO2 range follows the rise in PO2 which occurs after birth. The mechanism of this resetting is unknown. To study whether it is accompanied by a change in the carotid body microvasculature, 2 pairs of carotid bodies from fetal sheep (145 days gestation) and 2 pairs from 7-8 days-old lambs were examined. The ratio of the area of small vessels (6-16 microns diameter) or of larger vessels (greater than 16 microns diameter) to the total area of individual lobules of the carotid body was measured, using a semi-automatic image analysis system. This quantified the number and total cross-sectional area of small vessels and of larger vessels in 20 sections of 5 microns thickness taken at random from 200-350 sections cut from each carotid body. When the carotid bodies of the fetus and neonate were compared, the neonates showed increases in the percentage of the lobule area occupied by both small and large vessels, but the difference was only significant in the case of the larger vessels. There was no difference in the ratio of the area occupied by smaller vessels to the extravascular area of the lobule. Our results do not support the idea that the post-natal resetting of chemoreceptor sensitivity from the fetal to the post-natal range is accompanied by a change in the perfusion of the carotid body chemoreceptor cells.

Animals↗
PubMed2004

ATP is a key mediator of central and peripheral chemosensory transduction.

Recent evidence suggests that ATP is a mediator of central (within the ventral surface of the medulla) and peripheral (within the carotid body) chemosensory transduction. This short review discusses the data obtained in experiments in vivo and in vitro supporting this hypothesis. P2 receptors for ATP are expressed within the ventrolateral medulla as well as by the peripheral chemosensory afferent neurones. Blockade of P2 receptors in the ventrolateral medulla attenuates the CO2-induced increase in respiration while blockade of purinergic signalling impairs carotid body function and diminishes the ventilatory response to hypoxia. Furthermore, ATP is released from the ventral surface of the medulla during hypercapnia and from the carotid body during hypoxia. Finally, exogenous ATP applied on the ventral surface of the medulla evokes rapid increase in phrenic nerve activity, while ATP applied to the carotid body evokes marked excitation of the carotid sinus nerve afferents. We suggest that in the ventrolateral medulla ATP is produced following CO2/H(+)-induced activation of central chemosensory elements (neuronal and/or glial) and acts within the respiratory network to produce physiologically relevant changes in ventilation. In the carotid body, ATP contributes in a significant manner to the transmission of the sensitivity of the carotid body to changes in arterial PO2 and may be considered as a key transmitter released by chemoreceptor cells to activate endings of the sinus nerve afferent fibres.

Adenosine Triphosphate↗