Is there an Influence of Autonomic Nerves on Sensory Nerves in the Meninges? – Release of CGRP and PGE2 in vitro

To examine effects of development and chronic high-altitude hypoxia on sympathetic nerve function in sheep, norepinephrine release was measured in vitro from middle cerebral and facial arteries. Capsaicin was used to test the role of capsaicin-sensitive sensory nerves; norepinephrine release was not altered by capsaicin treatment. N ω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, decreased stimulation-evoked norepinephrine release in middle cerebral arteries from normoxic sheep with no effect in hypoxic arteries or facial arteries. Thus NO-releasing nerves augmented norepinephrine release. Furthermore, the function of NO-releasing nerves declined after chronic hypoxia. Despite loss of the augmenting effects of NO, stimulation-evoked fractional norepinephrine release was unchanged after chronic hypoxia, suggesting that middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a decline in stimulation-evoked norepinephrine release, but there was an increase in the adult facial artery. In the adult, adaptation to chronic hypoxia is similar in both cerebral and facial arteries. However, differential adaptation in fetal adrenergic nerves may reflect differences in fetal redistribution of blood flow in the face of chronic hypoxia but could also possibly contribute to increased incidence of fetal morbidity.

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LPS-sensory peptide communication in experimental cystitis

AJP Renal Physiology ◽

10.1152/ajprenal.0163.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. F202-F210 ◽

Cited By ~ 36

Author(s):

M. R. Saban ◽

R. Saban ◽

T. G. Hammond ◽

M. Haak-Frendscho ◽

H. Steinberg ◽

...

Keyword(s):

Neurogenic Inflammation ◽

Transforming Growth Factor ◽

Bladder Wall ◽

In Vitro Release ◽

Neutrophil Infiltration ◽

Interferon Γ ◽

Sensory Nerves ◽

Bladder Inflammation ◽

Leukocytic Infiltration

Stimulation of sensory nerves can lead to release of peptides such as substance P (SP) and consequently to neurogenic inflammation. We studied the role of bacterial lipopolysaccharide (LPS) in regulating SP-induced inflammation. Experimental cystitis was induced in female mice by intravesical instillation of SP, LPS, or fluorescein-labeled LPS. Uptake of fluorescein-labeled LPS was determined by confocal analysis, and bladder inflammation was determined by morphological analysis. SP was infused into the bladders of some mice 24 h after exposure to LPS. In vitro studies determined the capacity of LPS and SP to induce histamine and cytokine release by the bladder. LPS was taken up by urothelial cells and distributed systemically. Twenty-four hours after instillation of LPS or SP, bladder inflammation was characterized by edema and leukocytic infiltration of the bladder wall. LPS pretreatment enhanced neutrophil infiltration induced by SP, increased in vitro release of histamine, tumor necrosis factor-α, and interferon-γ, and significantly reduced transforming growth factor-β1 release. These findings suggest that LPS amplifies neurogenic inflammation, thereby playing a role in the pathogenesis of neurogenic cystitis.

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Interleukin-1β-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00363.2001 ◽

2002 ◽

Vol 283 (5) ◽

pp. L909-L917 ◽

Cited By ~ 21

Author(s):

Z.-X. Wu ◽

B. E. Satterfield ◽

J. S. Fedan ◽

R. D. Dey

Keyword(s):

Smooth Muscle ◽

Substance P ◽

Airway Smooth Muscle ◽

Airway Hyperresponsiveness ◽

Sensory Nerves ◽

Tracheal Smooth Muscle ◽

Fiber Density ◽

Smooth Muscle Contractility ◽

Neurokinin 1

Interleukin (IL)-1β causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1β. Ferrets were instilled intratracheally with IL-1β (0.3 μg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1β. The IL-1β-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1β-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1β. These results show that IL-1β-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.

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Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.3.1195 ◽

1993 ◽

Vol 74 (3) ◽

pp. 1195-1199 ◽

Cited By ~ 21

Author(s):

G. M. Verleden ◽

M. G. Belvisi ◽

K. F. Rabe ◽

M. Miura ◽

P. J. Barnes

Keyword(s):

Substance P ◽

Guinea Pig ◽

Electrical Field Stimulation ◽

Sensory Nerves ◽

Inhibitory Effects ◽

Exogenous Substance ◽

Dependent Inhibition ◽

Adrenoceptor Agonists ◽

Beta 2

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.

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Capsaicin-sensitive afferent nerves activate submucosal secretomotor neurons in guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.269.2.g203 ◽

1995 ◽

Vol 269 (2) ◽

pp. G203-G209 ◽

Cited By ~ 10

Author(s):

S. Vanner ◽

W. K. MacNaughton

Keyword(s):

Guinea Pig ◽

Ion Transport ◽

Short Circuit ◽

Ussing Chamber ◽

Sensory Nerve ◽

Nerve Fibers ◽

Sensory Nerves ◽

Guinea Pig Ileum ◽

Secretomotor Neurons

This study examined whether capsaicin-sensitive sensory nerves regulate intestinal ion transport using both Ussing chamber and intracellular recording techniques in in vitro submucosal preparations from the guinea pig ileum. In Ussing chamber studies, serosal application of capsaicin (20 nM-20 microM) evoked a biphasic dose-dependent increase in short-circuit current (Isc) (maximal effective concentration 200 nM and 2 microM, respectively). In chloride-free buffer, capsaicin responses were significantly reduced. Capsaicin evoked little or no response when extrinsic sensory nerve fibers had been surgically removed and tetrodotoxin and low-calcium and high-magnesium solutions blocked responses to capsaicin. In epithelial preparations devoid of submucosal neurons, capsaicin had virtually no effect, suggesting that responses evoked by capsaicin-sensitive nerves result from activation of submucosal secretomotor neurons. Intracellular recordings from single submucosal neurons demonstrated that superfusion with capsaicin (2 microM) depolarized neurons with an associated decreased conductance. Depolarizations were completely desensitized when capsaicin was reapplied, but synaptic inputs were unaffected. This study suggests that capsaicin-sensitive nerves can regulate ion transport in the gastrointestinal tract by release of neurotransmitter(s) that activate submucosal secretomotor neurons.

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Mechanism of action of capsaicin on submucosal arterioles in the guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.265.1.g51 ◽

1993 ◽

Vol 265 (1) ◽

pp. G51-G55 ◽

Cited By ~ 4

Author(s):

S. Vanner

Keyword(s):

Guinea Pig ◽

Mechanism Of Action ◽

Sensory Nerves ◽

Human Calcitonin ◽

Prostaglandin F2 Alpha ◽

Afferent Fibers ◽

Calcitonin Gene ◽

Muscarinic Receptor Antagonists ◽

Repeated Applications

Vasomotor neurons in the enteric nervous system release acetylcholine to dilate submucosal arterioles, but it is not known whether sensory nerves that project to these vessels also can provide a vasodilator innervation. This possibility was examined by determining the mechanism of action of capsaicin on guinea pig ileal submucosal arterioles in vitro. Capsaicin dilated all vessels that had been preconstricted with prostaglandin F2 alpha; mean effective concentration was 11 nM, and maximal dilation occurred at 60-200 nM. The vasodilation showed marked desensitization upon repeated applications of capsaicin. Tetrodotoxin blocked the capsaicin-induced vasodilation but not the desensitization observed upon repeated application. Muscarinic receptor antagonists did not affect the actions of capsaicin. Capsaicin did not dilate arterioles whose extrinsic sensory afferent fibers had been surgically removed. Substance P and human calcitonin gene-related peptide II dilated arterioles; these dilations were not inhibited after desensitization of the capsaicin-induced vasodilation. Thus capsaicin dilates submucosal arterioles by selectively activating extrinsic afferent fibers that release vasodilator transmitter substances onto these vessels.

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Neuro-immune interactions in chemical-induced airway hyperreactivity

European Respiratory Journal ◽

10.1183/13993003.01778-2015 ◽

2016 ◽

Vol 48 (2) ◽

pp. 380-392 ◽

Cited By ~ 18

Author(s):

Fien C. Devos ◽

Brett Boonen ◽

Yeranddy A. Alpizar ◽

Tania Maes ◽

Valérie Hox ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Transient Receptor Potential ◽

Chinese Hamster ◽

Transient Receptor Potential Channels ◽

Airway Hyperreactivity ◽

Sensory Nerves ◽

Wild Type ◽

Immunological Parameters

Asthma may be induced by chemical sensitisers,viamechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitrointracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using anin vivomodel, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, inTrpa1andTrpv1knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficientKitWsh/Wshmice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR.

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In vitro interactions between sensory nerves, epidermis, hair follicles and capillaries in a tissue-engineered reconstructed skin

Experimental Dermatology ◽

10.1111/j.0906-6705.2004.212bf.x ◽

2008 ◽

Vol 13 (9) ◽

pp. 582-582

Author(s):

V. Gagnon ◽

M. Gingras ◽

L. Germain ◽

H. D. Durham ◽

F. Berthod

Keyword(s):

Hair Follicles ◽

Sensory Nerves ◽

Reconstructed Skin ◽

In Vitro Interactions

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Sensory nerves directly promote osteoclastogenesis by secreting Cyp40

10.21203/rs.3.rs-1092196/v1 ◽

2021 ◽

Author(s):

Guo-Xian Pei ◽

Liu Yang ◽

Junqin Li ◽

Bin Liu ◽

Hao Wu ◽

...

Keyword(s):

Bone Resorption ◽

Bone Repair ◽

Bone Cells ◽

Critical Role ◽

Sensory Nerve ◽

Sensory Nerves ◽

Blue Staining ◽

Double Labeling ◽

Sensory Hypersensitivity

Abstract BackgroundGiven the afferent functions, sensors have been found exerting efferent influences and directly alter organ physiology. Sensory nerves have been found critical in osteoclasts and bone resorption. However, the direct evidence of whether sensory nerve efferent influences osteoclast, remains lacking. MethodsWe treated mice with resiniferatoxin (RTX) or complete Freund’s adjuvant (CFA) to induce sensory hypersensitivity. Bone histomorphometry including micro-ct, three-point bending assay, von kossa staining, calcein double labeling, toluidine blue staining, and trap staining were performed to monitor bone quality and bone cells. Multiple virus vectors were applied to trace signals between sensory nerves and osteoclasts. Sensory neurons (SN) and osteoclasts were cocultured to study the effects and mechanisms of the sensory nerves on osteoclasts in vitro. Isobaric tag for relative and absolute quantitation (iTRAQ) was used to identify secreted proteins in the sensory nerve. ResultsHere, we found sensory hypersensitivity significantly increased osteoclast bone resorption; SN directly promote osteoclastogenesis in vitro; and abundant sensory efferent signals transported into osteoclasts. Then our screening identified a novel neuropeptide Peptidyl-prolyl cis-trans isomerase D (Cyp40), is the reverse signal from the sensory nerve and plays a critical role for osteoclastogenesis, via aryl hydrocarbon receptor (AhR)-Ras/Raf-pErk-NFATc1 pathway. The efferent signals from sensory nerves tend to involves in the rapid feedback process: vast majority of sensory efferent signals (87.28%) present in fast-twitch myofibers. ConclusionThis study revealed a novel mechanism of sensory nerves on osteoclasts: the direct promotion of osteoclastogenesis by the Cyp40. This mechanism may represent a direct, and quick response of sensory nerves to the changes in bone. Targeting the Cyp40 could therefore be a strategy to promote bone repair at the early stage of bone injury.

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