Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries

Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes.

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Calcitonin Gene-Related Peptide and Cerebral Blood Vessels: Distribution and Vasomotor Effects

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1987.126 ◽

1987 ◽

Vol 7 (6) ◽

pp. 720-728 ◽

Cited By ~ 224

Author(s):

L. Edvinsson ◽

R. Ekman ◽

I. Jansen ◽

J. McCulloch ◽

R. Uddman

Keyword(s):

Substance P ◽

Guinea Pig ◽

Blood Vessels ◽

Mammalian Species ◽

Cerebral Arteries ◽

Nerve Fibers ◽

Neurokinin A ◽

Cerebral Blood Vessels ◽

Calcitonin Gene ◽

Basilar Arteries

The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are described for a number of different mammalian species. CGRP-immunoreactive nerve fibers were present in the adventitia of cerebral arteries in all species examined (guinea pig, cat, rabbit, rat, and mouse). Numerous perikarya containing CGRP immunoreactivity are demonstrable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal perikarya, CGRP is often colocalized with substance P and neurokinin A. Marked interspecies differences exist both in the density of CGRP-immunoreactive nerve fibers and in the cerebrovascular levels measured with radioimmunoassay. The highest concentrations were observed in cerebral vessels from guinea pigs, the lowest concentration in rabbit vessels, and intermediate levels in the feline and human cerebral vasculature. CGRP is a potent dilator of cerebral arteries in all species examined (human pial, feline middle cerebral, rabbit, guinea pig and rat basilar arteries). The concentration of CGRP eliciting half-maximal responses ranged from 0.4 n M (human pial artery) to 3 n M (rat and rabbit basilar arteries). Pretreatment of cerebral arteries with low concentrations of either substance P (0.1 n M) or neurokinin A (3 n M) attenuated slightly the CGRP-induced relaxations of guinea pig basilar arteries. Calcitonin was found to be a very weak dilator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP appear to be present in all mammalian species (although to varying degrees) and CGRP is invariably a potent dilator of the cerebral arteries for all species.

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Sensory Nerve Endings in the Mucosa of the Epiglottis—Morphologic Investigations with Silver Impregnation, Immunohistochemistry, and Electron Microscopy

Otolaryngology ◽

10.1177/019459988709600110 ◽

1987 ◽

Vol 96 (1) ◽

pp. 55-62 ◽

Cited By ~ 21

Author(s):

Takemoto Shin ◽

Shun Watanabe ◽

Shigeru Wada ◽

Tadatsugu Maeyama

Keyword(s):

Electron Microscopy ◽

Substance P ◽

Sensory Nerve ◽

Nerve Fibers ◽

Silver Impregnation ◽

Taste Bud ◽

Nerve Endings ◽

Electron Microscopic ◽

Sensory Nerve Endings ◽

Microscopic Studies

This study was conducted in order to investigate the structure of sensory nerve endings of the human epiglottis and substance P immunoreactive nerve fibers of the canine epiglottis in relationship to physiologic functions of the larynx. The human epiglottis was observed by light microscopy (silver impregnation) and electron microscopy, and the canine epiglottis was studied by peroxidase-anti-peroxidase (PAP) immunohistochemistry. The results are summarized as follows: (1) In the membranes of the epiglottis, we observed free endings of simple or complex tree shape, corpuscle endings with glomerular patterns, and taste-bud-like structures, and (2) electron microscopic studies revealed varicosity of the terminal axon with processes that contained small, clear and large, dense cored vesicles. Substance P was observed in these structures, and it was suggested that substance P was related to perception in the larynx.

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Susbstance P Levels in Children with Atopic Dermatitis

Berkala Ilmu Kesehatan Kulit dan Kelamin ◽

10.20473/bikk.v33.3.2021.182-186 ◽

2021 ◽

Vol 33 (3) ◽

pp. 182

Author(s):

Khairina Nasution ◽

Deryne Anggia Paramita ◽

Nova Zairina Lubis

Keyword(s):

Atopic Dermatitis ◽

Substance P ◽

Observational Study ◽

Sensory Nerve ◽

Skin Inflammation ◽

Nerve Fibers ◽

Cross Sectional ◽

Adolescent Group ◽

Group 12 ◽

Common Skin

Background: Atopic dermatitis (AD) is the most common skin disease in infants and children. AD is influenced by hereditary and environmental factors, and it is characterized by an inflammatory reaction in the skin. In developing countries, children suffering from AD are estimated around 10–20%, of which 60% of the cases persist into adulthood. Substance P is a cutaneous neuropeptide that contributes to the pathogenesis of AD. Substance P promotes the production of nerve growth factors from keratinocytes, and the release of histamine, leukotriene, or tumor necrosis factor from mast cells, which cause the growth of sensory nerve fibers, augmentation of skin inflammation, and are considered pruritogenic factors. Purpose: This study aims to determine the description of substance P in children with atopic dermatitis using a descriptive observational study with a cross-sectional approach. Methods: This is a destructive observational study with a crossectional approach samples were selected from AD patients at the Universitas Sumatera Utara Hospital. Result: The largest group of subjects were childhood (2–12 years old), there was 60%, followed by the adolescent group (12–18 years old) and the infant group (<2 years old). In the childhood group, the highest level of substance P was found in girls with a mean of 349.03 ± 146.7. On the other hand, the highest levels of substance P in the adolescent were found in males with a mean of 243.73 ± 64.57 ng/L. Conclusion: In this study, we found that the level of substance p was higher in the childhood group.

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Substance P (NK1) receptor immunoreactivity on endothelial cells of the rat tracheal mucosa

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.3.l404 ◽

1996 ◽

Vol 270 (3) ◽

pp. L404-L414 ◽

Cited By ~ 3

Author(s):

J. J. Bowden ◽

P. Baluk ◽

P. M. Lefevre ◽

S. R. Vigna ◽

D. M. McDonald

Keyword(s):

Endothelial Cells ◽

Substance P ◽

Direct Action ◽

Sensory Nerve ◽

Nerve Fibers ◽

Receptor Internalization ◽

Nk1 Receptor ◽

Tracheal Mucosa ◽

Nk1 Receptors ◽

Plasma Leakage

Substance P released from sensory nerve fibers causes plasma leakage through an action on neurokinin-1 (NK1 or substance P) receptors. However, it is unknown whether the leakage results from a direct action of substance P on endothelial cells. We determined the distribution of NK1 receptors at sites of plasma leakage in the rat tracheal mucosa, using NK1 receptor-immunoreactive endosomes as markers of substance P-induced receptor internalization. We found that immunoreactive endosomes were located in the endothelial cells of venules and capillaries but not in those of arterioles. Five minutes after vagal stimulation for 1 min, the number of immunoreactive endosomes in endothelial cells was increased 5-fold in postcapillary venules (mean of 17.4 endosomes/100 micron2 compared with a baseline value of 3.4), 15-fold in collecting venules (12.1 compared with 0.8), and 4-fold in capillaries (2.5 compared with 0.7). No endosomes were found in arterioles under either condition. The number of immunoreactive endosomes in individual vessels corresponded to the amount of stimulus-induced plasma leakage. Both the receptor internalization and the plasma leakage were blocked by the selective NK1 receptor antagonist SR-140333 (100 microgram/kg iv). Although both substance P (5 microgram/kg iv) and platelet-activating factor (5 microgram/kg iv) caused plasma leakage, only substance P induced receptor internalization. We conclude that substance P, released from sensory nerve fibers, causes plasma leakage through a direct action on endothelial cells of venules, and that this action is followed by the internalization of NK1 receptors into endosomes.

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Substance P Regulates Environmental Tobacco Smoke-Enhanced Tracheal Smooth Muscle Responsiveness in Mice

Journal of Allergy ◽

10.1155/2012/423612 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10

Author(s):

Lan Xiao ◽

Zhong-Xin Wu

Keyword(s):

Smooth Muscle ◽

Substance P ◽

Environmental Tobacco Smoke ◽

Tobacco Smoke ◽

Sensory Nerve ◽

Electrical Field Stimulation ◽

Underlying Mechanism ◽

Nerve Fibers ◽

Tracheal Smooth Muscle ◽

Airway Responses

Environmental tobacco smoke (ETS) is an environmental trigger that leads to airway inflammation and airway hyperresponsiveness (AHR) in susceptible individuals and animals, but the underlying mechanism is not fully understood. Substance P (SP) release from sensory nerve fibers has been linked to AHR. The present experiments characterize the role of SP in tracheal smooth muscle on ETS-increased airway responses. The mice were exposed to either sidestream tobacco smoke (SS), a surrogate to ETS, or filtered air (FA) for 1 day or 5 consecutive days. Contractions of tracheal smooth muscle to SP and electrical field stimulation (EFS) were not significantly altered in 1 of day SS-exposed mice. However, 5 of days SS exposure significantly increased airway smooth muscle contractions to SP and EFS. Administration of CP-99994, an antagonist of the neurokinin (NK)1 receptor, attenuates the SS exposure-enhanced tracheal smooth muscle responses to EFS. Furthermore, the immunohistochemistry showed that SP nerve fibers were increased in tracheal smooth muscle after 5 of days SS exposure. These results suggest that the increased SP production may contribute to SS-enhanced smooth muscle responsiveness in mice trachea.

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Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.1.r279 ◽

2001 ◽

Vol 281 (1) ◽

pp. R279-R290 ◽

Cited By ~ 33

Author(s):

Ulla C. Kopp ◽

Michael Z. Cicha ◽

Lori A. Smith ◽

Tomas Hökfelt

Keyword(s):

Nitric Oxide ◽

Substance P ◽

Sensory Nerve ◽

Receptor Activation ◽

Nerve Fibers ◽

Sensory Nerves ◽

Renal Nerve ◽

Inhibitory Neurotransmitter ◽

Pelvic Perfusion ◽

Pelvic Pressure

Nerve terminals containing neuronal nitric oxide synthase (nNOS) are localized in the renal pelvic wall where the sensory nerves containing substance P and calcitonin gene-related peptide (CGRP) are found. We examined whether nNOS is colocalized with substance P and CGRP. All renal pelvic nerve fibers that contained nNOS-like immunoreactivity (-LI) also contained substance P-LI and CGRP-LI. In anesthetized rats, renal pelvic perfusion with the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC, 20 μM) prolonged the afferent renal nerve activity (ARNA) response to a 3-min period of increased renal pelvic pressure from 5 ± 0.4 to 21 ± 2 min ( P < 0.01, n = 14). The magnitude of the ARNA response was unaffected byl-SMTC. Similar effects were produced by N ω-nitro-l-arginine methyl ester (l-NAME) but not d-NAME. Increasing renal pelvic pressure produced similar increases in renal pelvic release of substance P before and during l-SMTC, from 5.9 ± 1.4 to 13.6 ± 4.2 pg/min before and from 4.9 ± to 12.6 ± 2.7 pg/min during l-SMTC. l-SMTC also prolonged the ARNA response to renal pelvic perfusion with substance P (3 μM) from 1.2 ± 0.2 to 5.6 ± 1.1 min ( P < 0.01, n = 9) without affecting the magnitude of the ARNA response. In conclusion: activation of NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensory nerve fibers by mechanisms related to activation of substance P receptors.

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Axon typing of rat muscle nerves using a double staining procedure for cholinesterase and carbonic anhydrase.

Journal of Histochemistry & Cytochemistry ◽

10.1177/39.12.1719070 ◽

1991 ◽

Vol 39 (12) ◽

pp. 1617-1625 ◽

Cited By ~ 6

Author(s):

M J Szabolcs ◽

A Windisch ◽

R Koller ◽

M Pensch

Keyword(s):

Carbonic Anhydrase ◽

Cross Sections ◽

Sensory Nerve ◽

Histological Section ◽

Trapezius Muscle ◽

Motor Units ◽

Conventional Technique ◽

Nerve Fibers ◽

Staining Procedure ◽

Muscle Nerve

We developed a method for detecting activity of axonal cholinesterase (CE) and carbonic anhydrase (CA)--markers for motor and sensory nerve fibers (NFs)--in the same histological section. To reach this goal, cross-sections of muscle nerves were sequentially incubated with the standard protocols for CE and CA histochemistry. A modified incubation medium was used for CA in which Co++ is replaced by Ni++. This avoids interference of the two histochemical reactions because Co++ binds unspecifically to the brown copper-ferroferricyanide complex representing CE activity, whereas Ni++ does not. Cross-sections of the trapezius muscle nerve containing efferent and afferent NFs in segregated fascicles showed that CE activity was confined to motor NFs. Axonal CA was detected solely in sensory NFs. The number of labeled motor and sensory NFs determined in serial cross-sections stained with either the new or the conventional technique was not significantly different. Morphometric analysis revealed that small unreactive NFs (diameter less than 5 microns) are afferent, medium-sized ones (5 microns less than d less than 7 microns) are unclassifiable, and large ones (d greater than 7 microns) are efferent. The heterogenous CE activity of thick (alpha) motor NFs is linked to the type of their motor units. "Fast" motor units contain CE reactive NFs; "slow" ones have CE negative neurites.

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Prion Infection of Skeletal Muscle Cells and Papillae in the Tongue

Journal of Virology ◽

10.1128/jvi.78.13.6792-6798.2004 ◽

2004 ◽

Vol 78 (13) ◽

pp. 6792-6798 ◽

Cited By ~ 39

Author(s):

Ellyn R. Mulcahy ◽

Jason C. Bartz ◽

Anthony E. Kincaid ◽

Richard A. Bessen

Keyword(s):

Skeletal Muscle ◽

Sensory Nerve ◽

Meat Products ◽

Muscle Cells ◽

Nerve Fibers ◽

Skeletal Muscle Cells ◽

Lingual Papillae ◽

Intracerebral Inoculation ◽

Axon Terminals ◽

Prion Infection

ABSTRACT The presence of the prion agent in skeletal muscle is thought to be due to the infection of nerve fibers located within the muscle. We report here that the pathological isoform of the prion protein, PrPSc, accumulates within skeletal muscle cells, in addition to axons, in the tongue of hamsters following intralingual and intracerebral inoculation of the HY strain of the transmissible mink encephalopathy agent. Localization of PrPSc to the neuromuscular junction suggests that this synapse is a site for prion agent spread between motor axon terminals and muscle cells. Following intracerebral inoculation, the majority of PrPSc in the tongue was found in the lamina propria, where it was associated with sensory nerve fibers in the core of the lingual papillae. PrPSc staining was also identified in the stratified squamous epithelium of the lingual mucosa. These findings indicate that prion infection of skeletal muscle cells and the epithelial layer in the tongue can be established following the spread of the prion agent from nerve terminals and/or axons that innervate the tongue. Our data suggest that ingestion of meat products containing prion-infected tongue could result in human exposure to the prion agent, while sloughing of prion-infected epithelial cells at the mucosal surface of the tongue could be a mechanism for prion agent shedding and subsequent prion transmission in animals.

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Lumbosacral intersegmental epispinal axons and ectopic ventral nerve rootlets

Journal of Neurosurgery ◽

10.3171/jns.1987.67.2.0269 ◽

1987 ◽

Vol 67 (2) ◽

pp. 269-277 ◽

Cited By ~ 9

Author(s):

Wesley W. Parke ◽

Ryo Watanabe

Keyword(s):

Nerve Root ◽

Sensory Nerve ◽

Conus Medullaris ◽

Spinal Nerve ◽

Nerve Fibers ◽

Ventral Horn ◽

Spinal Nerve Roots ◽

Nerve Roots ◽

Content Type ◽

Almost All

✓ An epispinal system of motor axons virtually covers the ventral and lateral funiculi of the human conus medullaris between the L-2 and S-2 levels. These nerve fibers apparently arise from motor cells of the ventral horn nuclei and join spinal nerve roots caudal to their level of origin. In all observed spinal cords, many of these axons converged at the cord surface and formed an irregular group of ectopic rootlets that could be visually traced to join conventional spinal nerve roots at one to several segments inferior to their original segmental level; occasional rootlets joined a dorsal nerve root. As almost all previous reports of nerve root interconnections involved only the dorsal roots and have been cited to explain a lack of an absolute segmental sensory nerve distribution, it is believed that these intersegmental motor fibers may similarly explain a more diffuse efferent distribution than has previously been suspected.

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