SEARCH · PubMed Health

Results for “Chemoreceptor Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed1999

Differential effects of angiotensin II in the nucleus tractus solitarii of the rat--plausible neuronal mechanism.

1. Cellular mechanisms of the actions of angiotensin II (ANGII) within the nucleus of the solitary tract (NTS) were studied using rat brain slices in 78 neurones recorded in the whole-cell configuration. Twenty-nine per cent of cells had an on-going activity and with only one exception these cells responded to tractus solitarii (TS) stimulation with a monophasic excitatory postsynaptic potential (EPSP). In approximately half of the silent cells, TS stimulation evoked an EPSP-inhibitory postsynaptic potential (IPSP) complex. 2. The ANGII (200 or 1000 nM) effect on TS-evoked EPSPs depended on the cell subpopulation. In cells with on-going activity, ANGII (1000 nM) increased evoked EPSP amplitude by +70 +/- 13 % (means +/- s.e.m., n = 5) but reduced it (200 and 1000 nM) in silent cells where both evoked EPSPs and IPSPs were present. ANGII either increased TS-evoked IPSP conductances in cells where they were detectable or revealed an evoked IPSP (200 nM ANGII: IPSP conductance increased from 70 +/- 29 to 241 +/- 34 pS; n = 11). All ANGII effects were prevented by the ANGII type 1 (AT1) receptor blocker losartan. Since 200 nM ANGII did not increase responses to iontophoretically applied GABA, the effect of ANGII on TS-evoked IPSPs may occur presynaptically. 3. The neurokinin type 1 (NK1) receptor antagonist CP-99,994 (5 microM) blocked the ANGII-induced increase in EPSPs but had no effect on TS-evoked IPSP potentiation by ANGII. 4. Thus, ANGII can potentiate both inhibitory and excitatory synaptic transmission within different subpopulations of NTS neurones. Potentiation of evoked EPSPs, but not of IPSPs, involves activation of NK1 receptors. The balance of these actions of ANGII could be reflex specific: for the baroreflex circuitry the inhibitory action might predominate while the peripheral chemoreceptor reflex may be facilitated due to enhanced excitatory transmission.

Angiotensin II↗

PubMed2003

The C. elegans che-1 gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons.

Chemotaxis to water-soluble chemicals such as NaCl is an important behavior of C. elegans when seeking food. ASE chemosensory neurons have a major role in this behavior. We show that che-1, defined by chemotaxis defects, encodes a zinc-finger protein similar to the GLASS transcription factor required for photoreceptor cell differentiation in Drosophila, and that che-1 is essential for specification and function of ASE neurons. Expression of a che-1::gfp fusion construct was predominant in ASE. In che-1 mutants, expression of genes characterizing ASE such as seven-transmembrane receptors, guanylate cyclases and a cyclic-nucleotide gated channel is lost. Ectopic expression of che-1 cDNA induced expression of ASE-specific marker genes, a dye-filling defect in neurons other than ASE and dauer formation.

Amino Acid Sequence↗

PubMed2002

Innervation of the carotid body: Immunohistochemical, denervation, and retrograde tracing studies.

This review presents information about multiple neurochemical substances in the carotid body. Nerve fibers around blood vessels and glomus cells within the chemoreceptive organ contain immunoreactivities (IR) for tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), calretinin (CR), calbindin D-28k (CB), parvalbumin (PV), and nitric oxide synthase (NOS). Parasympathetic neurons scattered around the carotid body contain VIP, choline acetyltransferase, and vanilloid receptor 1-like receptor. In the mammalian carotid body, transection of the carotid sinus nerve (CSN) causes the absence or decrease of CGRP-, SP-, and NOS-immunoreactive (IR) nerve fibers, whereas all NPY-IR nerve fibers disappear after removal of the superior cervical ganglion. Most VIP-IR nerve fibers disappear but a few persist after sympathetic ganglionectomy. In addition, the CSN transection appears to cause the acquisition of GAL-IR in originally immunonegative glomus cells and nerve fibers within the rat carotid body. On the other hand, 4%, 25%, 17%, and less than 1% of petrosal neurons retrogradely labeled from the rat CSN contain TH-, CGRP-, SP-, and VIP-IR, respectively. In the chicken carotid body, many CGRP- and SP-IR nerve fibers disappear after vagus nerve transection or nodose ganglionectomy. GAL-, NPY-, and VIP-IR nerve fibers mostly disappear after removal of the 14th cervical ganglion of the sympathetic trunk. The origin and functional significance of the various neurochemical substances present in the carotid body is discussed.

Animals↗

PubMed1980

Changes in membrane potential and membrane fluidity in Tetrahymena pyriformis in association with chemoreception of hydrophobic stimuli: fluorescence studies.

The fluorescence intensity of rhodamine 6G (Rh6G) and 1,6-diphenyl-1,3,5-hexatriene (DPH) in the presence of Tetrahymena pyriformis was measured to monitor changes in the membrane potential and in the gross structure of the surface membrane in response to chemical stimuli. So-called "odorants" for higher vertebrates, which are usually uncharged and hydrophobic compounds, were chosen as chemical stimuli for a model study of the olfactory response. The fluorescence intensity of Rh6G started to increase at the chemotactic thresholds of the stimuli, indicating that negative chemotaxis of T. pyriformis to the hydrophobic stimuli is induced by depolarization of the cell. The fluorescence intensity of DPH increased in close association with chemoreception of the hydrophobic stimuli. The increase in the fluorescence intensity was ascribed mainly to uptake of DPH, suggesting that gross structural changes of the surface membrane occur with the reception of hydrophobic stimuli. The membrane fluidity determined by fluorescence polarization of DPH increased in close association with the chemoreception of the hydrophobic stimuli. Inorganic salts such as NcCl, KCl, and CaCl2 did not change the DPH fluorescence intensity or the fluorescence polarization, although these stimuli induced depolarization and negative chemotaxis in T. pyriformis.

Animals↗

PubMed1986

Discharge patterns of bulbar respiratory neurons in response to the morphinomimetic agent, fentanyl, in chloralosed dogs.

In anaesthetized, paralysed and artificially ventilated dogs, activities were recorded from the phrenic nerve and from respiratory units within the nucleus tractus solitarii (nTS), the nucleus ambiguus (nA) and the nucleus retroambigualis (nRA). The respiratory neurons were classified according to their discharge pattern and their response to lung inflation. Fentanyl injected into the vertebral artery (0.5-2 micrograms/kg) or intravenously (10 micrograms/kg) produced a depressant effect on the phrenic nerve motoneurons, on inspiratory cells (I alpha and I beta) and on phase-spanning expiratory-inspiratory neurons of the nTS and the nA. The duration of the inspiratory burst increased and the number of spikes and the peak activity were reduced. This pattern of inhibition was followed by complete blockade of spike genesis. Fentanyl also altered expiratory neurons: the duration of the expiratory discharge was enhanced. An increase followed by a decrease in the number of spikes per burst and a reduction in the peak activity were observed. When the phrenic nerve was silent, continuous discharges appeared. High doses of fentanyl were needed to inhibit these tonic discharges. This pattern of inhibition concerns late peak expiratory units, expiratory units with a constant discharge pattern and the phase-spanning inspiratory-expiratory neurons. Naloxone antagonized these effects but induced the appearance of tonic discharges in fentanyl-treated phase-spanning expiratory-inspiratory neurons. Stimulation of peripheral chemoreceptors with almitrine (0.2 mg/kg i.v.) antagonized the effects of fentanyl. In addition, fentanyl facilitated the lung inflation reflex on respiratory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed2004

Saccharin stimulates the "deterrent" cell in the blowfly: behavioral and electrophysiological evidence.

In the attempt to gain more information on the mechanisms underlying bitter and/or sweet taste reception, we have investigated the responses of labellar chemosensilla in the blowfly Protophormia terraenovae to Na-saccharin, as compared to sweet stimuli (sucrose or fructose) and bitter stimuli (denatonium benzoate or amiloride). Electrophysiological and behavioral results indicate that the sweetener Na-saccharin inhibits the "sugar" cell in the labellar taste sensilla of the blowfly P. terraenovae. In multichoice preference tests, flies ingested more of the solutions containing sugar to those with sugar+Na-saccharin. This finding is in good agreement with the spike frequency reduction observed for the "sugar" cell activity. Analysis of the spike discharges also shows a positive dose-response for the "deterrent" cell following stimulation with Na-saccharin and denatonium benzoate. Flies drank any of the Na-saccharin solutions, regardless of their concentration, less than water, thus indicating a weak deterring effect on water drinking. The prevailing activation of the "deterrent" cell by stimulation with Na-saccharin is not directly coupled with a coherent behavioral output. Cross adaptation was found to occur between responses to Na-saccharin and denatonium benzoate or amiloride regardless of the order of adapting stimuli. In the case of sweet stimuli, cross adaptation occurred when the adapting stimulus was Na-saccharin, but it did not when the adapting stimuli were sucrose or fructose. Addition of Na-saccharin to both sugars significantly depressed the spike firing frequency, while an increase was observed with denatonium benzoate or amiloride.

Animals↗

PubMed1990

Independent components of the neural population response for discrimination of quality and intensity of chemical stimuli.

The responses of a population of 30 olfactory receptor cells from spiny lobsters to 8 behaviorally relevant complex types of stimuli at 0.005, 0.05 and 0.5 mM were analyzed using multidimensional scaling to evaluate their potential for coding quality and intensity. A discrimination index was derived from the resulting stimulus coordinates, which takes into account the response similarities within type/concentration and the response dissimilarities between types/concentrations. The results indicate that quality and intensity can be discriminated by separate components of the response of the population of neurons: quality by the pattern of responses produced across the neuronal population, and intensity by the absolute response magnitude.

Animals↗

PubMed1993

Localization of NADPH diaphorase in neurons of the rostral ventral medulla: possible role of nitric oxide in central autonomic regulation and oxygen chemoreception.

We studied whether neurons containing nitric oxide synthase (NOS) are localized to the rostral ventrolateral medulla (RVM) and, if so, whether they are distinct from the adrenergic neurons of the C1 group. NOS-containing neurons and/or C1 neurons were visualized using NADPH diaphorase histochemistry and phenylethanolamine N-methyltransferase (PNMT) immunohistochemistry, respectively. A column of NADPH diaphorase-positive neurons, extending 2 mm in the rostrocaudal plane, was observed lateral to the inferior olive and medial to the C1 neurons. Double labelling studies showed that NADPH diaphorase-positive neurons were not immunoreactive for PNMT, indicating that the two enzymes were localized in the different cells. Furthermore, only a small fraction of NADPH diaphorase neurons were retrogradely labelled after injections of fluorogold into the thoracic cord. We conclude that the RVM contains a well-defined group of neurons endowed with NOS that are distinct from the adrenergic neurons of the C1 group and have only limited monosynaptic projections to the spinal cord. Since the RVM is involved in the control of arterial pressure and in oxygen-conserving reflexes, the findings raise the possibility that nitric oxide participates in central autonomic regulation and oxygen chemoreception.

Animals↗

PubMed1986

The promise of enzymes in therapy of hyperlipidemia.

Treatment of hyperlipidemias must be commenced in that intestinal segment where alimentary lipoprotein aggregate generation is initiated postprandially and the aggregates are still in nascent form. This is to prevent the formation of potentially pathological units that do not equilibrate with the blood colloid. The colloid chemical state of the alimentary lipoprotein entities in the systemic circulation is decisive for maintenance of their stability and for their disposal from the blood. The causes of impaired, "unripe," lipoprotein aggregate formation include: (a) the action of human pancreatic lipase is even normally a restricted and vulnerable process, (b) inadequate ratio of protein to fat to stabilize the aggregates, (c) defective proteolysis in the small intestine, and (d) the dual behavior of the surface tension-lowering agent, the lecithin antagonist cholesterol. On the one hand, cholesterol represents physicochemically the weakest link in the lipoprotein interfaces. On the other hand, an excess of cholesterol in lipoprotein interfaces decreases the stability of the surface film. This leads to changes in the decay of the entities and the cell surface-active lipid constituents of the "unripe" plasma lipoprotein colloid complexes can easily be adsorbed to the endothelial cell surface plasma membrane: the excess aggregate-cholesterol molecules simply join, or dissolve in, the cell membrane-cholesterol which thus acts as its own receptor or solvent: cholesterol dimers occur. This causes rigidity of the endothelial cell surface membrane and leads to impaired cell metabolism. The intima recognizes the impairment as a foreign body and initiates a physiological defense reaction including phagocytosis. The event may be still more dangerous if the adrenergic receptors of the autonomous nervous system involved in lipolysis with subsequent plasma efflux are simultaneously stimulated. The therapeutic measure indicated is production of balanced alimentary lipoprotein aggregates. This can be achieved by oral administration of (a) protease, and (b) non-specific micellar lipase. The lipase functions without restriction and can perform all the activities that human pancreatic lipase cannot. The enzymes utilized are of mold origin and generally available.

Adipose Tissue↗

PubMed1997

Effect of CO on VO2 of carotid body and chemoreception with and without Ca2+.

This study was done using high PCO (> 500 Torr at PO2 of 120 Torr) in the carotid body perfusate in vitro, and recording simultaneously the activity of the whole carotid sinus nerve (CSN) and VO2 of the carotid body. In the cascade of excitation of CSN by high PCO in the dark [light eliminated the excitation; S. Lahiri, News Physiol. Sci. 9 (1992) 161-165], Ca2+ effects occur at the level of neurosecretion after the level of oxygen consumption, according to the following scheme: CO-hypoxia-->VO2 decrease-->K+ conductance decrease-->cell depolarization-->cytosolic Ca2+ rise-->neurosecretion-->neural discharge. Thus, a part of the hypothesis was that [Ca2+] decrease, being a downstream event, may not affect VO2 of the carotid body. Also, to determine to what extent the intracellular calcium stores contribute to cystolic [Ca2+] and chemosensory discharge with high PCO, we tested the effect of interruption of perfusate flow with medium nominally free of [Ca2+] on CSN excitation and VO2 of the carotid body with and without high PCO. High PCO in the dark decreased carotid body VO2, independent of [Ca2+]o. CSN excitation was always enhanced by high PCO, and its sensitivity to perfusate flow interruption. Also, nominally Ca(2+)-free solution increased the latency and decreased the rate of rise and peak activity of CSN during interruption of perfusate flow, but CO augmented the responses. This reversal effect by CO suggests that Ca2+ is released from intracellular stores, because CO has no other way to excite the chemoreceptors than by acting on the intracellular stores.

Animals↗

PubMed2004

Cilium-attached and excised patch-clamp recordings of odourant-activated Ca-dependent K channels from chemosensory cilia of olfactory receptor neurons.

It has previously been proposed that a Ca2+-dependent K+ conductance is implicated in the inhibitory odourant response in rat and toad olfactory receptor neurons. Previous whole-cell and single-channel measurements on inside-out excised patches, in addition to immunochemical evidence, indicated the presence of Ca2+-dependent K+ channels in olfactory cilia, the transducing structures of these sensory cells. Ca2+-dependent K+ channels opened in 'on-cilium' membrane patches from C. caudiverbera upon odourant stimulation. Furthermore, after excision in the inside-out configuration, the channel could be opened by micromolar Ca2+, in a Ca2+-dependent fashion, but it was unresponsive to cyclic AMP. We estimated that the Ca2+ concentration in the proximity of a Ca2+-dependent K+ channel within the cilia reaches at least 100 microM during the odour response. The K+ channel displayed a higher selectivity for K+ than for Na+. Our results support a role for this Ca2+-dependent K+ channel in chemotransduction.

Animals↗

PubMed1980

Rat supraoptic neurones: the effects of locally applied hypertonic saline.

1. Extracellular action potentials were recorded from supraoptic neurones in lactating, urethane-anaesthetized rats. A microtap was used to apply a very small volume (about 10(-7) ml.) of hypertonic saline (1-4 M-NaCl) to the immediate neighbourhood of these units over about 1 min.2. Twenty-five of twenty-seven supraoptic neurones were excited by this local osmotic stimulus. The response of individual units was reversible and repeatable. Microtap applications of isotonic saline to supraoptic neurones were without observed effect.3. Continuously firing supraoptic neurones responded to hypertonic saline with a smooth acceleration in firing rate. Phasic neurones showed an increase in the over-all level of activity, and in particular, a prolongation of the active phases. Slow, irregularly firing cells responded either with a smooth acceleration in firing rate, or with phasic behaviour.4. The response to local hypertonic saline appears to be reasonably specific to the supraoptic nucleus. Of thirty-five neurones recorded close to the supraoptic nucleus but which were not antidromically activated from stimulation of the neural stalk, only nine responded to the local application of hypertonic saline.5. Similarities between the manner of response of supraoptic neurones to local application of hypertonic saline and the manner of their response to systemic increases in the osmotic pressure of blood plasma support the hypothesis that supraoptic neurones are osmosensitive.

Action Potentials↗

PubMed2005

Genetic analysis of the HAMP domain of the Aer aerotaxis sensor localizes flavin adenine dinucleotide-binding determinants to the AS-2 helix.

HAMP domains are signal transduction domains typically located between the membrane anchor and cytoplasmic signaling domain of the proteins in which they occur. The prototypical structure consists of two helical amphipathic sequences (AS-1 and AS-2) connected by a region of undetermined structure. The Escherichia coli aerotaxis receptor, Aer, has a HAMP domain and a PAS domain with a flavin adenine dinucleotide (FAD) cofactor that senses the intracellular energy level. Previous studies reported mutations in the HAMP domain that abolished FAD binding to the PAS domain. In this study, using random and site-directed mutagenesis, we identified the distal helix, AS-2, as the component of the HAMP domain that stabilizes FAD binding. AS-2 in Aer is not amphipathic and is predicted to be buried. Mutations in the sequence coding for the contiguous proximal signaling domain altered signaling by Aer but did not affect FAD binding. The V264M residue replacement in this region resulted in an inverted response in which E. coli cells expressing the mutant Aer protein were repelled by oxygen. Bioinformatics analysis of aligned HAMP domains indicated that the proximal signaling domain is conserved in other HAMP domains that are not involved in chemotaxis or aerotaxis. Only one null mutation was found in the coding sequence for the HAMP AS-1 and connector regions, suggesting that these are not active signal transduction sites. We consider a model in which the signal from FAD is transmitted across a PAS-HAMP interface to AS-2 or the proximal signaling domain.

Adenylyl Cyclases↗

PubMed2002

Calcium transients in the garter snake vomeronasal organ.

The signaling cascade involved in chemosensory transduction in the VN organ is incompletely understood. In snakes, the response to nonvolatile prey chemicals is mediated by the vomeronasal (VN) system. Using optical techniques and fluorescent Ca(2+) indicators, we found that prey-derived chemoattractants produce initially a transient cytosolic accumulation of [Ca(2+)](i) in the dendritic regions of VN neurons via two pathways: Ca(2+) release from IP(3)-sensitive intracellular stores and, to a lesser extent, Ca(2+) influx through the plasma membrane. Both components seem to be dependent on IP(3) production. Chemoattractants evoke a short-latency Ca(2+) elevation even in the absence of extracellular Ca(2+), suggesting that in snake VN neurons, Ca(2+) release from intracellular stores is independent of a preceding Ca(2+) influx, and both components are activated in parallel during early stages of chemosensory transduction. Once the response develops in apical dendritic segments, other mechanisms can also contribute to the amplification and modulation of these chemoattractant-mediated cytosolic Ca(2+) transients. In regions close to the cell bodies of the VN neurons, the activation of voltage-sensitive Ca(2+) channels and a Ca(2+)-induced Ca(2+) release from intracellular ryanodine-sensitive stores secondarily boost initial cytosolic Ca(2+) elevations increasing their magnitude and durations. Return of intracellular Ca(2+) to prestimulation levels appears to involve a Ca(2+) extrusion mediated by a Na(+)/Ca(2+) exchanger mechanism that probably plays an important role in limiting the magnitude and duration of the stimulation-induced Ca(2+) transients.

Animals↗

PubMed1993

Responses of rat medullary dorsal horn neurons following intranasal noxious chemical stimulation: effects of stimulus intensity, duration, and interstimulus interval.

1. Most quantitative examinations of nociception are performed with thermal or mechanical stimuli. Because nociceptive processing mechanisms may depend on the modality of the stimuli, comparable studies on chemonociception are necessary. 2. We examined the activity of chemonociceptive medullary dorsal horn neurons in halothane-anesthetized rats. For controlled noxious chemical stimulation, defined CO2 pulses were applied to the nasal mucosa. The effects of stimulus intensity, duration, and interstimulus interval (ISI) were tested by performing three different CO2 stimulation protocols (see below). 3. The recorded neurons were characterized by intranasal and facial stimuli of different modalities. The cells received input from intranasal A delta- and/or C-fibers. All tested neurons also responded to other intranasally applied irritants, e.g., mustard oil. Furthermore, the units were sensitive to intranasal high-threshold mechanical stimulation and to facial mechanical stimulation. According to the properties of their facial mechanoreceptive fields, the units were classified as wide dynamic range (WDR) or nociceptive specific (NS) neurons. The majority of the cells also responded to facially applied noxious heat stimuli, so that most of the recorded neurons were found to be multimodal. Some of the neurons, in addition, had convergent input from primary afferents innervating the maxillary tooth pulps or the cornea and periorbital structures. 4. In the first stimulation protocol we presented four different CO2 concentrations (25, 50, 75, and 100%; stimulus duration 2 s). In total, each concentration was applied 10 times (2 trains of 5 stimuli). Stimulus response functions (SRFs) were computed with average responses to identical stimuli. All but 2 of the 23 tested neurons displayed enhanced responses after stimulation with increasing intensities. In general, WDR cells (n = 15) discharged more vigorously to the same CO2 concentration than NS cells (n = 8). WDR neurons discriminated more reliably between stimulus intensities in the low to moderate range (25-50% CO2) than NS cells. Both categories of neurons, however, discriminated equally well in the moderate- to high-intensity range (50-75% CO2). The discriminatory capacity of WDR and NS neurons was reduced in the highest concentration range (75-100% CO2). The proportion of NS neurons significantly discriminating between these intensities tended to be higher compared with WDR neurons when stimuli were applied with long ISIs (120 s). 5. To examine the effects of the duration of the ISI, identical test sequences were performed with ISIs of 30 and 120 s. (ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed2006

Male pheromone protein components activate female vomeronasal neurons in the salamander Plethodon shermani.

BACKGROUND: The mental gland pheromone of male Plethodon salamanders contains two main protein components: a 22 kDa protein named Plethodon Receptivity Factor (PRF) and a 7 kDa protein named Plethodon Modulating Factor (PMF), respectively. Each protein component individually has opposing effects on female courtship behavior, with PRF shortening and PMF lengthening courtship. In this study, we test the hypothesis that PRF or PMF individually activate vomeronasal neurons. The agmatine-uptake technique was used to visualize chemosensory neurons that were activated by each protein component individually. RESULTS: Vomeronasal neurons exposed to agmatine in saline did not demonstrate significant labeling. However, a population of vomeronasal neurons was labeled following exposure to either PRF or PMF. When expressed as a percent of control level labeled cells, PRF labeled more neurons than did PMF. These percentages for PRF and PMF, added together, parallel the percentage of labeled vomeronasal neurons when females are exposed to the whole pheromone. CONCLUSION: This study suggests that two specific populations of female vomeronasal neurons are responsible for responding to each of the two components of the male pheromone mixture. These two neural populations, therefore, could express different receptors which, in turn, transmit different information to the brain, thus accounting for the different female behavior elicited by each pheromone component.

Animals↗

PubMed1999

The C. elegans homeodomain gene unc-42 regulates chemosensory and glutamate receptor expression.

Genes that specify cell fate can influence multiple aspects of neuronal differentiation, including axon guidance, target selection and synapse formation. Mutations in the unc-42 gene disrupt axon guidance along the C. elegans ventral nerve cord and cause distinct functional defects in sensory-locomotory neural circuits. Here we show that unc-42 encodes a novel homeodomain protein that specifies the fate of three classes of neurons in the Caenorhabditis elegans nervous system: the ASH polymodal sensory neurons, the AVA, AVD and AVE interneurons that mediate repulsive sensory stimuli to the nematode head and anterior body, and a subset of motor neurons that innervate head and body-wall muscles. unc-42 is required for the expression of cell-surface receptors that are essential for the mature function of these neurons. In mutant animals, the ASH sensory neurons fail to express SRA-6 and SRB-6, putative chemosensory receptors. The AVA, AVD and AVE interneurons and RME and RMD motor neurons of unc-42 mutants similarly fail to express the GLR-1 glutamate receptor. These results show that unc-42 performs an essential role in defining neuron identity and contributes to the establishment of neural circuits in C. elegans by regulating the transcription of glutamate and chemosensory receptor genes.

Amino Acid Sequence↗

PubMed1994

Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat.

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes. Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B. The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-kappa B from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity. The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed.

Astrocytes↗