Neurokinin-1 Receptors Modulate the Excitability of Expiratory Neurons in the Ventral Respiratory Group

2008 ◽  
Vol 99 (2) ◽  
pp. 900-914 ◽  
Author(s):  
Angelina Y. Fong ◽  
Jeffrey T. Potts
Keyword(s):  
Substance P ◽  
Respiratory Rhythm ◽  
Firing Frequency ◽  
Unit Recording ◽  
Ventral Respiratory Group ◽  
Before And After ◽  
Expiratory Neurons ◽  
Neurokinin 1 ◽  
Endogenous Release

We studied the role of neurokinin-1 receptors (NK1-R) on the excitability of expiratory (E) neurons (tonic discharge, ETONIC; augmenting, EAUG; decrementing, EDEC) throughout the ventral respiratory group, including Bötzinger Complex (BötC) using extracellular single-unit recording combined with pressurized picoejection in decerebrate, arterially perfused juvenile rats. Responses evoked by picoejection of the NK1-R agonist, [Sar9-Met(O2)11]-substance P (SSP) were determined before and after the selective NK1-R antagonist, CP99,994. SSP excited 20 of 35 expiratory neurons by increasing the number of action potentials per burst (+33.7 ± 6.5% of control), burst duration (+20.6 ± 7.9% of control), and peak firing frequency (+16.2 ± 4.8% of control; means ± SE). Pretreatment with CP99,994 completely blocked SSP-evoked excitation in a subset of neurons tested, supporting the notion that SSP excitation was mediated through NK1-R activation. Because we had previously shown that EAUG neurons were crucial to locomotor-respiratory coupling (LRC), we reasoned that blockade of NK1-R would alter LRC by preventing somatic-evoked excitation of EAUG neurons. Blockade of NK1-Rs by CP99,994 in the BötC severely disrupted LRC and prevented somatic-evoked excitation of EAUG neurons. These findings demonstrate that LRC is dependent on endogenous SP release acting via NK1-Rs on EAUG neurons of the BötC. Taken together with our earlier finding that inspiratory off-switching by the Hering-Breuer Reflex requires endogenous activation of NK1-Rs through activation of NK1-Rs on EDEC neurons, we suggest that endogenous release of substance P in the BötC provides a reflex pathway-dependent mechanism to selectively modulate respiratory rhythm.

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

2007 ◽  
Vol 292 (4) ◽  
pp. L915-L923 ◽  
Author(s):  
Jaime Chávez ◽  
Patricia Segura ◽  
Mario H. Vargas ◽  
José Luis Arreola ◽  
Edgar Flores-Soto ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Smooth Muscle Contraction ◽  
In Vivo Experiments ◽  
Intracellular Ca ◽  
Neurokinin 1 ◽  
Substance P Release

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Functional role of ventral respiratory group expiratory neurons during vocalization

1996 ◽  
Vol 26 (3) ◽  
pp. 225-233 ◽  
Author(s):  
Akihiro Katada ◽  
Toshihiko Sugimoto ◽  
Kazue Utsumi ◽  
Satoshi Nonaka ◽  
Takashi Sakamoto
Keyword(s):  
Functional Role ◽  
Ventral Respiratory Group ◽  
Expiratory Neurons

The Role of Substance P in the Marginal Division of the Neostriatum in Learning and Memory is Mediated Through the Neurokinin 1 Receptor in Rats

2011 ◽  
Vol 36 (10) ◽  
pp. 1896-1902 ◽  
Author(s):  
Xue-mei Liu ◽  
Si Yun Shu ◽  
Chang-chun Zeng ◽  
Ye-feng Cai ◽  
Kui-hua Zhang ◽  
...  
Keyword(s):  
Substance P ◽  
Learning And Memory ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Marginal Division

Plasma Changes of Calcitonin Gene-Related Peptide and Substance P in Patients with Dialysis Headache

Cephalalgia ◽  
2006 ◽  
Vol 26 (11) ◽  
pp. 1287-1293 ◽  
Author(s):  
M Alessandri ◽  
L Massanti ◽  
P Geppetti ◽  
G Bellucci ◽  
M Cipriani ◽  
...  
Keyword(s):  
Substance P ◽  
Plasma Concentrations ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Biochemical Factor ◽  
Before And After ◽  
Basal Plasma ◽  
Headache Patients

Little is known of mechanism of dialysis headache (DH). As suggested for migraine, a role for neuropeptides has been investigated. Twenty-four patients under haemodialysis were studied. Twelve of them suffered from DH. The remaining patients were headache free. Blood samples for radioimmunoassay of calcitonin gene-related peptide (CGRP) and substance P (SP) were collected from the arteriovenous fistula before and after dialysis treatment. Basal plasma concentrations of CGRP were found to be higher in headache patients. Dialysis significantly decreased CGRP concentrations in both groups. No difference in basal plasma concentrations of SP was observed between groups. At the end of the treatment plasma SP concentrations were reduced in headache-free patients but increased in headache patients. Elevated plasma concentrations of CGRP in patients with DH could represent a biochemical factor contributing to susceptibility to headache. Because of the disputable role of SP in migraine, the significance of the increase of the peptide in plasma during DH remains to be elucidated.

scholarly journals Elevated Neurokinin 1-Receptor Expression in uterine products of conception is associated with first trimester Miscarriages

2020 ◽  
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Adeel Haider Tirmazi ◽  
Fridoon Jawad Ahmad ◽  
...  
Keyword(s):  
Substance P ◽  
First Trimester ◽  
Receptor Expression ◽  
Diagnostic Biomarkers ◽  
Neurokinin 1 Receptor ◽  
Products Of Conception ◽  
Mother’S Age ◽  
Neurokinin 1 ◽  
First Time

AbstractBackgroundMiscarriage is a common complication of early pregnancy, mostly occurring in first trimester. However, the etiological factors, prognostic and diagnostic biomarkers are not well known. Neurokinin-1 Receptor (NK-1R) is a receptor of tachykinin peptide, Substance P (SP) and has a role in various pathological conditions, cancers but it’s association with miscarriages and significance as a clinicopathological parameter is not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception. Role of NK-1R is not known in miscarriages.Materials and MethodsNK-1R expression was assessed in products of conception by immunohistochemistry. Protein expression was evaluated using the nuclear labelling index (%).ResultsTen human products of conception tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of POCs. NK-1R expression showed no notable differences among different cases of miscarriages irrespective of the mother’s age and gestational age at which the event occurred.ConclusionsExpression of NK-1R was similar in all the cases and it was intense. It shows that dysregulation of NK-1R along with its ligand Substance P might be involved in miscarriages. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time, the expression and localization of NK-1R in products of conception. We suggest NK-1R antagonist in addition to the Immunoglobulins and Human chorionic gonadotropin, to diagnose and treat spontaneous miscarriages.

Control of abdominal and expiratory intercostal muscle activity during vomiting: role of ventral respiratory group expiratory neurons

1987 ◽  
Vol 57 (6) ◽  
pp. 1854-1866 ◽  
Author(s):  
A. D. Miller ◽  
L. K. Tan ◽  
I. Suzuki
Keyword(s):  
Muscle Activity ◽  
Discharge Rate ◽  
Abdominal Muscle ◽  
Lumbar Spinal Cord ◽  
Abdominal Muscles ◽  
Ventral Respiratory Group ◽  
Before And After ◽  
The One ◽  
Lumbar Spinal

The role of ventral respiratory group (VRG) expiratory (E) neurons in the control of abdominal and internal intercostal (expiratory) muscle activity during vomiting was examined in decerebrate cats by recording from these neurons during fictive vomiting in paralyzed animals and comparing abdominal muscle activity during vomiting before and after sectioning the axons of these descending neurons. Fictive vomiting was defined by a series of bursts of coactivation of abdominal and phrenic nerves elicited by either subdiaphragmatic vagus nerve stimulation or emetic drugs. Such coordinated activity would be expected to produce vomiting if the animals were not paralyzed. Data were recorded from 27 VRG E neurons that were antidromically activated from the lower thoracic (T13) or lumbar spinal cord. During fictive vomiting, almost two-thirds of these neurons (17/27) were mainly active in between periods of abdominal and phrenic nerve coactivation, when the internal intercostal motoneurons are known to be active. This group of neurons was termed INT neurons. INT neurons were subdivided according to whether they were active between every burst of phrenic and abdominal nerve coactivation (INTa neurons, n = 10) or only between some bursts (INTb neurons, n = 7). Another one-third of the VRG E neurons had normal or increased levels of activity when the abdominal nerves were active during fictive vomiting (ABD neurons). The one remaining neuron was mainly silent throughout fictive vomiting. ABD neurons were indistinguishable from INT neurons on the basis of their location in the VRG, type of firing pattern (ramp versus step ramp), conduction velocity, or extent of projection in the lumbar cord. However, INTa neurons had a significantly higher discharge rate during respiration than either ABD or INTb neurons. Abdominal muscle EMG and nerve activity were recorded from six unparalyzed cats before and after cutting the axons of VRG E neurons as they cross the midline between C1 and the obex. The lesions abolished or almost eliminated expiratory modulation of abdominal muscle activity. In contrast, the abdominal muscles were always active during vomiting; however, the amplitude of postlesion abdominal activity varied from approximately 70-100% of prelesion values in three cats to 60-70% of normal in a fourth animal to only approximately 20% of prelesion values in two other cats.(ABSTRACT TRUNCATED AT 400 WORDS)

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