Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

2008 ◽  
Vol 294 (3) ◽  
pp. L544-L552 ◽  
Author(s):  
Qihai Gu ◽  
Michelle E. Wiggers ◽  
Gerald J. Gleich ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Direct Action ◽  
Input Resistance ◽  
Sensory Nerves ◽  
Lung Inflation ◽  
Cationic Proteins ◽  
C Fibers ◽  
Current Clamp Mode ◽  
Sensitizing Effect ◽  
Isolated Rat

It has been shown that airway exposure to eosinophil-derived cationic proteins stimulated vagal pulmonary C fibers and markedly potentiated their responses to lung inflation in anesthetized rats (Lee LY, Gu Q, Gleich GJ, J Appl Physiol 91: 1318–1326, 2001). However, whether the effects resulted from a direct action of these proteins on the sensory nerves was not known. The present study was therefore carried out to determine the effects of these proteins on isolated rat vagal pulmonary sensory neurons. Our results obtained from perforated whole cell patch-clamp recordings showed that pretreatment with eosinophil major basic protein (MBP; 2 μM, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked ∼10 min after MBP and lasted for >60 min; in current-clamp mode, MBP substantially increased the number of action potentials evoked by both capsaicin and electrical stimulation. Pretreatment with MBP did not significantly alter the input resistance of these sensory neurons. In addition, the sensitizing effect of MBP was completely abolished when its cationic charge was neutralized by mixing with a polyanion, such as low-molecular-weight heparin or poly-l-glutamic or poly-l-aspartic acid, before its delivery to the neurons. Moreover, a similar sensitizing effect was also generated by other eosinophil granule-derived proteins (e.g., eosinophil peroxidase). These results demonstrate a direct, charge-dependent, and long-lasting sensitizing effect of cationic proteins on pulmonary sensory neurons, which may contribute to the airway hyperresponsiveness associated with airway infiltration of eosinophils under pathophysiological conditions.

scholarly journals Effects of human eosinophil granule-derived cationic proteins on C-fiber afferents in the rat lung

2001 ◽  
Vol 91 (3) ◽  
pp. 1318-1326 ◽  
Author(s):  
Lu-Yuan Lee ◽  
Qihai Gu ◽  
Gerald J. Gleich
Keyword(s):  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Human Eosinophil ◽  
Lung Inflation ◽  
Cationic Proteins ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
Eosinophil Granule

Experiments were performed to test the hypothesis that human eosinophil granule-derived cationic proteins stimulate vagal C-fiber afferents in the lungs and elicit pulmonary chemoreflex responses in anesthetized Sprague-Dawley rats. Intratracheal instillation of eosinophil cationic protein (ECP; 1–2 mg/ml, 0.1 ml) consistently induced an irregular breathing pattern, characterized by tachypnea (change in breathing frequency of 44.7%) and small unstable tidal volume (Vt). The tachypnea, accompanied by decreased heart rate and arterial blood pressure, started within 30 s after the delivery of ECP and lasted for >30 min. These ECP-induced cardiorespiratory responses were completely prevented by perineural capsaicin treatment of both cervical vagi, which selectively blocked C-fiber conduction, suggesting the involvement of these afferents. Indeed, direct recording of single-unit activities of pulmonary C-fibers further demonstrated that the same dose of ECP evoked a pronounced and sustained (>30-min) stimulatory effect on pulmonary C-fibers. Furthermore, the sensitivity of these afferents to lung inflation was also markedly elevated after the ECP instillation, whereas the vehicle of ECP administered in the same manner had no effect. Other types of eosinophil granule cationic proteins, such as major basic protein and eosinophil peroxidase, induced very similar respiratory and cardiovascular reflex responses. In conclusion, these results show that eosinophil granule-derived cationic proteins induce a distinct stimulatory effect on vagal pulmonary C-fiber endings, which may play an important role in the airway hyperresponsiveness associated with eosinophil infiltration in the airways.

Effect of increasing temperature on TRPV1-mediated responses in isolated rat pulmonary sensory neurons

2008 ◽  
Vol 294 (3) ◽  
pp. L563-L571 ◽  
Author(s):  
Dan Ni ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Direct Action ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Positive Interaction ◽  
C Fibers ◽  
Ganglion Neurons ◽  
Increasing Temperature

Hyperthermia has been shown to sensitize vagal pulmonary C-fibers in anesthetized rats. However, it was not clear whether the effect was due to a direct action of hyperthermia on these sensory neurons. To answer this question, we carried out this study to determine the effect of increasing temperature on the responses to various chemical stimuli in isolated nodose and jugular ganglion neurons innervating the rat lungs. In the whole cell perforated patch-clamp study, when the temperature was increased from normal (∼36°C) to hyperthermic (∼40.6°C) level of the rat body temperature, the inward currents evoked by capsaicin, a selective activator of the transient receptor potential vanilloid type 1 (TRPV1), and 2-aminoethoxydiphenyl borate (2-APB), a nonselective activator of TRPV1–3 receptors, were both significantly increased. This potentiating effect was clearly present even at a moderate level of hyperthermia (∼39°C). However, only the slow, sustained component of acid-evoked current mediated through the TRPV1 receptor was potentiated by hyperthermia, whereas the rapid, transient component was inhibited. In contrast, the currents evoked by adenosine 5′-triphosphate and acetylcholine, neither of which is known to activate the TRPV1 channel, did not increase when the same temperature elevation was applied. Furthermore, the hyperthermia-induced potentiation of the cell response to 2-APB was significantly attenuated by either capsazepine or AMG 9810, selective TRPV1 antagonists. In conclusion, increasing temperature within the physiological range exerts a potentiating effect on the response to TRPV1 activators in these neurons, which is probably mediated through a positive interaction between hyperthermia and these chemical activators at the TRPV1 channel.

scholarly journals Sensitizing effects of chronic exposure and acute inhalation of ovalbumin aerosol on pulmonary C fibers in rats

2008 ◽  
Vol 105 (1) ◽  
pp. 128-138 ◽  
Author(s):  
Guangfan Zhang ◽  
Ruei-Lung Lin ◽  
Michelle E. Wiggers ◽  
Lu-Yuan Lee
Keyword(s):  
Right Atrial ◽  
Brown Norway ◽  
Lung Inflation ◽  
Inflammatory Reactions ◽  
C Fibers ◽  
C Fiber ◽  
Inhalation Challenge ◽  
Sensitizing Effect ◽  
And Control ◽  
Norway Rats

The effect of ovalbumin (Ova) sensitization on pulmonary C-fiber sensitivity was investigated. Brown-Norway rats were sensitized by intraperitoneal injection of Ova followed by aerosolized Ova three times per week for 3 wk. Control rats received the vehicle. At the end of the third week, single-unit fiber activities (FA) of pulmonary C fibers were recorded in anesthetized, artificially ventilated rats. Our results showed the following: 1) Ova sensitization induced airway inflammation (infiltration of eosinophils and neutrophils) and airway hyperresponsiveness in rats; 2) baseline FA in sensitized rats was significantly higher than that in control ones; 3) similarly, the pulmonary C-fiber response to right atrial injection of capsaicin was markedly higher in sensitized rats, which were significantly amplified after the acute Ova inhalation challenge; and 4) similar patterns, but smaller magnitudes of the differences in C-fiber responses to adenosine and lung inflation, were also found between sensitized and control rats. In conclusion, Ova sensitization elevated the baseline FA and excitability of pulmonary C fibers, and the hypersensitivity was further potentiated after the acute Ova inhalation challenge in sensitized rats. Chronic allergic inflammatory reactions in the airway probably contributed to the sensitizing effect on these lung afferents.

scholarly journals Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of β3-adrenoceptor

2007 ◽  
Vol 102 (4) ◽  
pp. 1545-1555 ◽  
Author(s):  
Qihai Gu ◽  
You-Shuei Lin ◽  
Lu-Yuan Lee
Keyword(s):  
Right Atrial ◽  
Intracellular Camp ◽  
Lung Inflation ◽  
Adrenoceptor Antagonist ◽  
C Fibers ◽  
Baseline Activity ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Sensitizing Effect ◽  
Ganglion Neurons

This study was carried out to determine whether epinephrine alters the sensitivity of rat vagal sensory neurons. In anesthetized rats, inhalation of epinephrine aerosol (1 and 5 mg/ml, 3 min) induced an elevated baseline activity of pulmonary C fibers and enhanced their responses to lung inflation (20 cmH2O, 10 s) and right atrial injection of capsaicin (0.5 μg/kg). In isolated rat nodose and jugular ganglion neurons, perfusion of epinephrine (3 μM, 5 min) alone did not produce any detectable change of the intracellular Ca2+ concentration. However, immediately after the pretreatment with epinephrine, the Ca2+ transients evoked by chemical stimulants (capsaicin, KCl, and ATP) were markedly potentiated; for example, capsaicin (50 nM, 15 s)-evoked Ca2+ transient was increased by 106% after epinephrine ( P < 0.05; n = 11). The effect of epinephrine was mimicked by either BRL 37344 (5 μM, 5 min) or ICI 215,001 (5 μM, 5 min), two selective β3-adrenoceptor agonists, and blocked by SR 59230A (5 μM, 10 min), a selective β3-adrenoceptor antagonist, whereas pretreatment with phenylephrine (α1-adenoceptor agonist), guanabenz (α2-adrenoceptor agonist), dobutamine (β1-adrenoceptor agonist), or salbutamol (β2-adrenoceptor agonist) had no significant effect on capsaicin-evoked Ca2+ transient. Furthermore, pretreatment with SQ 22536 (100–300 μM, 15 min), an adenylate cyclase inhibitor, and H89 (3 μM, 15 min), a PKA inhibitor, completely abolished the potentiating effect of epinephrine. Our results suggest that epinephrine enhances the excitability of rat vagal chemosensitive neurons. This sensitizing effect of epinephrine is likely mediated through the activation of β3-adrenoceptor and intracellular cAMP-PKA signaling cascade.

Calcium transient evoked by nicotine in isolated rat vagal pulmonary sensory neurons

2007 ◽  
Vol 292 (1) ◽  
pp. L54-L61 ◽  
Author(s):  
Jennings Xu ◽  
Wenbin Yang ◽  
Guangfan Zhang ◽  
Qihai Gu ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Calcium Transient ◽  
Sensory Nerves ◽  
Right Atrial ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
C Fibers ◽  
Intracellular Ca ◽  
Intense Burst

It has been shown that inhaled cigarette smoke activates vagal pulmonary C fibers and rapidly adapting receptors (RARs) in the airways and that nicotine contained in the smoke is primarily responsible. This study was carried out to determine whether nicotine alone can activate pulmonary sensory neurons isolated from rat vagal ganglia; the response of these neurons was determined by fura-2-based ratiometric Ca2+ imaging. The results showed: 1) Nicotine (10−4 M, 20 s) evoked a transient increase in intracellular Ca2+ concentration ([Ca2+]i) in 175 of the 522 neurons tested (Δ[Ca2+]i = 142.2 ± 12.3 nM); the response was reproducible, with a small reduction in peak amplitude in the same neurons when the challenge was repeated 20 min later. 2) A majority (59.7%) of these nicotine-sensitive neurons were also activated by capsaicin (10−7 M). 3) 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP; 10−4 M, 20 s), a selective agonist of the neuronal nicotinic acetylcholine receptors (NnAChRs), evoked a pattern of response similar to that of nicotine. 4) The responses to nicotine and DMPP were either totally abrogated or markedly attenuated by hexamethonium (10−4 M). 5) In anesthetized rats, right atrial bolus injection of nicotine (75–200 μg/kg) evoked an immediate (latency <1–2 s) and intense burst of discharge in 47.8% of the pulmonary C-fiber endings and 28.6% of the RARs tested. In conclusion, nicotine exerts a direct stimulatory effect on vagal pulmonary sensory nerves, and the effect is probably mediated through an activation of the NnAChRs expressed on the membrane of these neurons.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

The Role of Plant-Derived Compounds in Managing Diabetes Mellitus: A Review of Literature from 2014 To 2019

2020 ◽  
Vol 28 ◽  
Author(s):  
Heba A.S. El-Nashar ◽  
Nada M. Mostafa ◽  
Mohamed El-Shazly ◽  
Omayma A. Eldahshan
Keyword(s):  
Diabetes Mellitus ◽  
Glycogen Synthase ◽  
Direct Action ◽  
Tyrosine Phosphatase ◽  
Natural Compounds ◽  
Antidiabetic Activity ◽  
Peroxisome Proliferator ◽  
Dipeptidyl Peptidase 4 ◽  
Glut4 Expression ◽  
Sensitizing Effect

Background:: Diabetes mellitus (DM) represents a global health problem characterized by hyperglycemia due to insufficient insulin secretion or failure of insulin activity. There is an imperative need for the discovery of alternative therapeutic agents that overcome the drawbacks of the current synthetic antidiabetic drugs. Objectives:: This review critically summarizes the reports on the known and novel natural compounds including alkaloids, flavonoids, and saponins with a potent antidiabetic activity that were recently published from 2014 to 2019. We discussed the underlying mechanisms of action that put these compounds in the category of effective antidiabetic candidates. Methods: Information was obtained from Google Scholar, Scirus, PubMed, and Science Direct. Discussion and Conclusion:: The reported natural compounds showed promising antidiabetic activity through different mechanisms such as the inhibition of α-amylase, α-glucosidase, insulin-sensitizing effect, direct action on protein tyrosine phosphatase 1B (PTP1B), peroxisome proliferator-activated receptors (PPARs), GLUT4 expression, insulin receptor substrate- 1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) as well as dipeptidyl peptidase-4 (DPP-4) enzyme. Some compounds inhibited the formation of advanced glycation end products (AGEs). Other compounds prevented the risk of diabetic complications such as cardiovascular diseases, retinopathy, and nephropathy. This review provides a critical overview of the most recent discoveries of antidiabetic agents from natural sources. This overview could help researchers to focus on the most prominent candidates aiming to develop new drug leads.

scholarly journals Functional subgroups of rat and human sensory neurons: a systematic review of electrophysiological properties

2022 ◽  
Author(s):  
Jannis Körner ◽  
Angelika Lampert
Keyword(s):  
Systematic Review ◽  
Action Potential ◽  
Sensory Neurons ◽  
Input Resistance ◽  
Immune Reactivity ◽  
Electrophysiological Properties ◽  
Electrophysiological Data ◽  
Electrophysiological Studies ◽  
Dorsal Root Ganglia Neurons ◽  
Definition Of

AbstractSensory neurons are responsible for the generation and transmission of nociceptive signals from the periphery to the central nervous system. They encompass a broadly heterogeneous population of highly specialized neurons. The understanding of the molecular choreography of individual subpopulations is essential to understand physiological and pathological pain states. Recently, it became evident that species differences limit transferability of research findings between human and rodents in pain research. Thus, it is necessary to systematically compare and categorize the electrophysiological data gained from human and rodent dorsal root ganglia neurons (DRGs). In this systematic review, we condense the available electrophysiological data defining subidentities in human and rat DRGs. A systematic search on PUBMED yielded 30 studies on rat and 3 studies on human sensory neurons. Defined outcome parameters included current clamp, voltage clamp, cell morphology, pharmacological readouts, and immune reactivity parameters. We compare evidence gathered for outcome markers to define subgroups, offer electrophysiological parameters for the definition of neuronal subtypes, and give a framework for the transferability of electrophysiological findings between species. A semiquantitative analysis revealed that for rat DRGs, there is an overarching consensus between studies that C-fiber linked sensory neurons display a lower action potential threshold, higher input resistance, a larger action potential overshoot, and a longer afterhyperpolarization duration compared to other sensory neurons. They are also more likely to display an infliction point in the falling phase of the action potential. This systematic review points out the need of more electrophysiological studies on human sensory neurons.

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