Neuropeptides and nasal secretion

1991 ◽  
Vol 261 (4) ◽  
pp. L223-L235 ◽  
Author(s):  
J. N. Baraniuk ◽  
M. Kaliner
Keyword(s):  
Nasal Mucosa ◽  
Defense Mechanism ◽  
Sensory System ◽  
Sensory Nerve ◽  
Sympathetic Nerves ◽  
Mucosal Injury ◽  
Sensory Nerves ◽  
Neurokinin A ◽  
Sympathetic Nervous Systems ◽  
Glandular Secretion

The nasal mucosa is innervated by the sensory, parasympathetic, and sympathetic nervous systems. Nociceptive sensory nerves are stimulated by mucosal injury, inhalation of irritants, or mast cell degranulation and release of the calcitonin gene-related peptide, the tachykinins substance P and neurokinin A, and other peptides by the axon response mechanism. Sensory nerve stimulation initiates systemic reflexes, such as the sneeze, and central parasympathetic reflexes which release acetylcholine, vasoactive intestinal peptide, and other peptides and lead to glandular secretion. In concert, these proinflammatory neural responses lead to vasodilation, vascular permeability, and glandular secretion. Sympathetic nerves release neuropeptide Y and norepinephrine, potent vasoconstrictors which act to decompress the nasal mucosa and produce nasal patency. The balance between the effects of parasympathetic and sympathetic neurotransmitters may regulate nasal homeostasis, whereas the nociceptive sensory system may be held in reserve as a defense mechanism. Dysfunction of these systems may lead to pathological nasal syndromes. In the future, specific neuropeptide agonists and antagonists may be useful for the treatment of human rhinitic diseases.

Relationships between permeable vessels, nerves, and mast cells in rat cutaneous neurogenic inflammation

1990 ◽  
Vol 68 (6) ◽  
pp. 2305-2311 ◽  
Author(s):  
J. N. Baraniuk ◽  
M. L. Kowalski ◽  
M. A. Kaliner
Keyword(s):  
Electrical Stimulation ◽  
Mast Cells ◽  
Neurogenic Inflammation ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Neurokinin A ◽  
Rat Skin ◽  
Protein Extravasation ◽  
Stimulation Of

Electrical stimulation of rat sensory nerves produces cutaneous vasodilation and plasma protein extravasation, a phenomenon termed “neurogenic inflammation”. Rat skin on the dorsum of the paw developed neurogenic inflammation after electrical stimulation of the saphenous nerve. In tissue sections, the extravasation of the supravital dye monastral blue B identified permeable vessels. Mast cells were identified by toluidine blue stain. Permeable vessels were significantly more dense in the superficial 120 microns of the dermis than in the deeper dermis, whereas mast cells were significantly more frequent in the deeper dermis. The relationships between nociceptive sensory nerve fibers, permeable vessels, and mast cells were examined by indirect immunohistochemistry for calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and substance P (SP). CGRP-, NKA-, and SP-containing nerves densely innervated the superficial dermis and appeared to innervate the vessels that became permeable during neurogenic inflammation. In contrast, mast cells were not associated with either permeable vessels or nerve fibers. These data suggest that electrical stimulation of rat sensory nerves produces vascular permeability by inducing the release of neuropeptides that may directly stimulate the superficial vascular bed. Mast cells may not be involved in this stage of cutaneous neurogenic inflammation in rat skin.

Sympathetic but not sensory denervation stimulates white adipocyte proliferation

2006 ◽  
Vol 291 (6) ◽  
pp. R1630-R1637 ◽  
Author(s):  
Michelle T. Foster ◽  
Timothy J. Bartness
Keyword(s):  
Sensory Nerve ◽  
Sympathetic Nerves ◽  
Cell Number ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Fat Cell ◽  
Protein Marker ◽  
White Adipocyte ◽  
Sensory Denervation

White adipocyte proliferation is a hallmark of obesity, but it largely remains a mechanistic mystery. We and others previously demonstrated that surgical denervation of white adipose tissue (WAT) triggers increases in fat cell number, but it is unknown whether this was due to preadipocyte proliferation or maturation of existing preadipocytes that allowed them to be counted. In addition, surgical denervation severs not only sympathetic but also sensory innervation of WAT. Therefore, we tested whether sympathetic WAT denervation triggers adipocyte proliferation using 5-bromo-2′-deoxyuridine (BrdU) as a marker of proliferation and quantified BrdU-immunoreactive (ir) cells that were colabeled with AD-3-ir, an adipocyte-specific membrane protein marker. The unilateral denervation model was used for all experiments where Siberian hamster inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham denervated serving as a within-animal control, and then BrdU was injected systemically for 6 days. When IWAT was surgically denervated, severing both sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker, were significantly decreased, and BrdU+AD-3-ir adipocytes were increased ∼300%. When IWAT was selectively sensory denervated via local microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH-ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was selectively sympathetically denervated via local microinjections of 6-hydroxy-dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was significantly decreased, and BrdU+AD-3-ir adipocytes were increased ∼400%. Collectively, these data provide the first direct evidence that sympathetic nerves inhibit white adipocyte proliferation in vivo.

Tachykinins, sensory nerves, and asthma—an overview

1995 ◽  
Vol 73 (7) ◽  
pp. 908-914 ◽  
Author(s):  
Jan M. Lundberg
Keyword(s):  
Viral Infections ◽  
Therapeutic Potential ◽  
Leukocyte Adhesion ◽  
Sensory Nerve ◽  
Neutral Endopeptidase ◽  
Sensory Nerves ◽  
Neurokinin A ◽  
Protein Extravasation ◽  
Neurokinin Receptor ◽  
Neurokinin 1

Tachykinin peptides, substance P (SP) and neurokinin A (NKA), are released from airway sensory nerves upon exposure to irritant chemicals and endogenous agents including bradykinin, prostaglandins, histamine, and protons. The released neuropeptides are potent inducers of a cascade of responses, including vasodilatation, mucus secretion, plasma protein extravasation, leukocyte adhesion–activation, and bronchoconstriction. Neurokinin 1 receptors (preferably activated by SP) seem to be most important for inflammatory actions, while neurokinin 2 receptors (preferably activated by NKA) mediate bronchoconstriction. Species differences exist whereby rat and guinea-pig have a more developed neurogenic inflammation response than normal human airways. However, disease states such as inflammation or viral infections lead to enhanced peptide synthesis and (or) increased sensory nerve excitability. Together with increased neurokinin 1 receptor synthesis and loss of major tachykinin-degrading enzymes such as neutral endopeptidase in airway inflammation, this suggests that recently developed, orally active nonpeptide neurokinin receptor antagonists could have a therapeutic potential in asthmatic patients.Key words: neurokinins, sensory nerves, inflammation, bronchoconstriction, receptors.

scholarly journals Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

2013 ◽  
Vol 304 (8) ◽  
pp. R675-R682 ◽  
Author(s):  
Jan Mulder ◽  
Tomas Hökfelt ◽  
Mark M. Knuepfer ◽  
Ulla C. Kopp
Keyword(s):  
Substance P ◽  
Optical Density ◽  
Renal Denervation ◽  
Time Course ◽  
Sympathetic Nerves ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Multiple Time ◽  
Sensory Reinnervation ◽  
Renal Sympathetic

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation.

Intranasal Toxicity of BMS-181885, A Novel 5-HT1 Agonist

1999 ◽  
Vol 18 (5) ◽  
pp. 285-296
Author(s):  
Gene E. Schulze ◽  
Jim E. Proctor ◽  
Mark A. Dominick ◽  
Amy E. Weiss ◽  
Oliver P. Flint ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nasal Mucosa ◽  
Olfactory Epithelium ◽  
Mucosal Injury ◽  
Separate Experiment ◽  
Toxic Metabolite ◽  
Respiratory Epithelial Cells ◽  
Nasal Injury ◽  
Respiratory Epithelial ◽  
Dose Dependent

One-month intranasal toxicity studies were conducted with BMS-181885 at doses of 1.5, 9, or 15 mg/animal/day in rats and 4, 24, or 40 mg/animal/day in monkeys. A 1-month intermittent intranasal toxicity study was also conducted in monkeys at doses of 3, 6, and 12 mg/animal 3 days per week. BMS-181885 was generally well tolerated in rats but resulted in dose-dependent nasal mucosal injury, primarily characterized by subacute inflammation of the nasal mucosa, and degeneration, single-cell necrosis, and/or erosion of the olfactory epithelium and, to a lesser extent, the respiratory epithelium. In monkeys, daily BMS-181885 administration was well tolerated and produced similar dose-dependent nasal injury primarily characterized by subacute inflammation of the nasal mucosa with degeneration and erosion of the olfactory epithelium. In a separate experiment, intermittent administration also resulted in dose-dependent nasal injury. In cultured rat nasal mucosal cells, BMS-181885 was toxic to olfactory epithelial cells with a range of mean IC50s between 44 and 291 μM. In contrast, BMS-181885 had no effect on respiratory epithelial cells up to its maximum solubility. Cytochrome P450 inhibition had no effect on the toxicity of BMS-181885 in olfactory epithelial cells but produced dose-dependent toxicity in respiratory epithelial cells, which was not present previously. The in vitro data suggest that parent drug, rather than a toxic metabolite, caused the drug-associated nasal mucosal injury.

Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Leon J DeLalio
Keyword(s):  
Heart Rate ◽  
Renovascular Hypertension ◽  
Sensory Nerve ◽  
Experimental Models ◽  
Sensory Nerves ◽  
Male Rats ◽  
Wild Type ◽  
Renal Nerve ◽  
Trpv1 Channels ◽  
Arterial Blood

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

Very Early Neurophysiological Study in Guillain-Barre Syndrome

2018 ◽  
Vol 80 (1-2) ◽  
pp. 100-105 ◽  
Author(s):  
Jiaoting Jin ◽  
Fangfang Hu ◽  
Xing Qin ◽  
Xuan Liu ◽  
Min Li ◽  
...  
Keyword(s):  
Nerve Conduction ◽  
Nerve Conduction Velocity ◽  
Tibial Nerve ◽  
Early Stage ◽  
Motor Nerve ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Motor Nerve Conduction ◽  
Abnormal Rate ◽  
Motor Nerves

Purpose: The diagnosis of Guillain-Barre syndrome (GBS) in the very early stage may be challenging. Our aim was to report the neurophysiological abnormalities in GBS within 4 days of clinical onset. We expected that GBS will be diagnosed by the assistance of neurophysiological study in the very early stage. Methods: We prospectively recruited patients with a diagnosis of GBS discharged from First Affiliated Hospital of Xi’an Jiaotong University and Xi Jing Hospital. Patients were classified into 3 groups according to the onset of symptoms to electromyography examination interval (OEI). The neurophysiological findings were carried out using standard procedures. All patients were examined by the same experienced neurophysiologist. Results: There were not significant group differences in abnormal rate, distal motor latency (DML), motor nerve conduction velocity (MNCV), F response (FR), compound muscle action potential (CMAP), conduction block (CB), sensory nerve action potential (SNAP), and sensory nerve conduction velocity among OEI ≤4 days, 4< OEI ≤10 days, and OEI > 10 days groups. Motor nerves were more affected than sensory nerves in neurophysiological presentation in very early stage patients. The difference of motor nerves and sensory nerves was statistically significant in lower limbs, but was not in upper limbs. In motor nerve conduction studies, the abnormal rate of DML, MNCV, FR, CB was more common seen in ulnar and peroneal nerve than median and tibial nerve, the abnormal rate of CMAP was the same in ulnar, median, peroneal and tibial nerve. In sensory nerve conduction studies, the abnormal rate of ulnar nerve and median nerve was higher than the superficial peroneal nerve and sural nerve. The OEI was not correlated with the SNAP decrease rate of median (r = 0.10, p = 0.23) and ulnar (r = 0.26, p = 0.06) but was statistically correlated with sural SNAP decrease rate (r = 0.29, p = 0.04). The sural-sparing pattern phenomenon was the most commonly discovered phenomenon in very early stage patients (OEI ≤4 days), followed by patients with 4< OEI ≤10 days, ultimately found in patients with OEI > 10 days. Conclusions: We suggest performing neurophysiological examination as soon as possible for suspected GBS patients, particularly focusing on multi-spots inspection of ulnar and peroneal nerves, and paying close attention to sural-sparing patterns.

Substance P and Neurokinin A in Human Nasal Mucosa

1991 ◽  
Vol 4 (3) ◽  
pp. 228-236 ◽  
Author(s):  
James N. Baraniuk ◽  
Jens D. Lundgren ◽  
Michiko Okayama ◽  
Julie Goff ◽  
Joaquim Mullol ◽  
...  
Keyword(s):  
Substance P ◽  
Nasal Mucosa ◽  
Neurokinin A ◽  
Human Nasal Mucosa

scholarly journals TrkA inhibitor promotes motor functional regeneration of recurrent laryngeal nerve by suppression of sensory nerve regeneration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroshi Suzuki ◽  
Koji Araki ◽  
Toshiyasu Matsui ◽  
Yuya Tanaka ◽  
Kosuke Uno ◽  
...  
Keyword(s):  
Recurrent Laryngeal Nerve ◽  
Nerve Regeneration ◽  
Vocal Fold ◽  
Compound Muscle Action Potential ◽  
Motor Nerve ◽  
Sensory Nerve ◽  
Laryngeal Nerve ◽  
Sensory Nerves ◽  
Nucleus Ambiguus ◽  
Functional Regeneration

Abstract Recurrent laryngeal nerve (RLN) injury, in which hoarseness and dysphagia arise as a result of impaired vocal fold movement, is a serious complication. Misdirected regeneration is an issue for functional regeneration. In this study, we demonstrated the effect of TrkA inhibitors, which blocks the NGF-TrkA pathway that acts on the sensory/automatic nerves thus preventing misdirected regeneration among motor and sensory nerves, and thereby promoting the regeneration of motor neurons to achieve functional recovery. RLN axotomy rat models were used in this study, in which cut ends of the nerve were bridged with polyglycolic acid-collagen tube with and without TrkA inhibitor (TrkAi) infiltration. Our study revealed significant improvement in motor nerve fiber regeneration and function, in assessment of vocal fold movement, myelinated nerve regeneration, compound muscle action potential, and prevention of laryngeal muscle atrophy. Retrograde labeling demonstrated fewer labeled neurons in the vagus ganglion, which confirmed reduced misdirected regeneration among motor and sensory fibers, and a change in distribution of the labeled neurons in the nucleus ambiguus. Our study demonstrated that TrkAi have a strong potential for clinical application in the treatment of RLN injury.

Neuropeptide Y is a vasoconstrictor in human nasal mucosa

1992 ◽  
Vol 73 (5) ◽  
pp. 1867-1872 ◽  
Author(s):  
J. N. Baraniuk ◽  
P. B. Silver ◽  
M. A. Kaliner ◽  
P. J. Barnes
Keyword(s):  
Neuropeptide Y ◽  
Protein Content ◽  
Vascular Permeability ◽  
Nasal Mucosa ◽  
Total Protein ◽  
Nerve Fibers ◽  
Human Nasal Mucosa ◽  
Nasal Provocation ◽  
Glandular Secretion ◽  
Nasal Secretions

Neuropeptide Y (NPY) is a neurotransmitter in sympathetic nerve fibers in human nasal mucosa. Like norepinephrine, NPY acts as a vasoconstrictor. An established method of nasal provocation was used to determine the effects of topically applied NPY on nasal resistance to airflow measured by anterior rhinomanometry, the protein content of nasal secretions, and the protein content of bradykinin-induced secretions. NPY (2.3 nmol) reduced the resistance to inspiratory airflow by 57 +/- 18% (P < 0.001) in 10 normal subjects and by 50 +/- 17% (P < 0.05) in 12 subjects with perennial rhinitis. In nasal provocations, NPY in doses of 0.1–10 nmol had no effect on vascular (albumin), glandular (lysozyme, glycoconjugate), or total proteins present in lavaged nasal secretions. Because the vasoconstrictor properties of NPY may only be apparent in the presence of increased vascular permeability and albumin exudation, bradykinin (BK) nasal provocation was performed. BK (500 nmol) significantly increase total protein (10- to 20-fold), albumin (10- to 30-fold), and glycoconjugate (2- to 5-fold) in lavage fluid. NPY (2.3 nmol) reduced BK-induced total protein by 59 +/- 15% (P < 0.05) and albumin by 63 +/- 17% (P < 0.02) but had no significant effect on glandular secretion. Therefore exogenous administration of NPY to the human nasal mucosa reduced nasal airflow resistance and albumin exudation without affecting submucosal gland secretion. NPY agonists may be useful for the treatment of mucosal diseases characterized by vasodilation, vascular permeability, and plasma exudation.

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