Both neurokinin A and substance P bind to NK1 receptors in guinea-pig lung

1989 ◽  
Vol 1 (4) ◽  
pp. 201-203 ◽  
Author(s):  
E. Burcher ◽  
D.J. Watkins ◽  
N.M. O'Flynn
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Neurokinin A ◽  
Nk1 Receptors

Tachykinin recovery during postmortem bronchoconstriction in guinea pig lungs

1991 ◽  
Vol 70 (3) ◽  
pp. 1215-1219 ◽  
Author(s):  
M. A. Martins ◽  
S. A. Shore ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Neutral Endopeptidase ◽  
Neurokinin A ◽  
Opening Pressure ◽  
Airway Opening ◽  
Isolated Lungs ◽  
Peak Value

We examined the role of substance P (SP) and neurokinin A (NKA) in the postmortem bronchoconstriction in guinea pig lungs using isolated lungs superfused via the trachea. Airway opening pressure (Pao) during superfusion was monitored and the superfusate collected for analysis of SP- and NKA-like immunoreactivities (SP-LI and NKA-LI, respectively). Peak Pao (39.0 +/- 3.9 cmH2O) was reached 10 min after starting superfusion; Pao decreased slowly thereafter, reaching only 9.9 +/- 2.2% of the peak value 2 h after starting superfusion (P less than 0.005); 12.6 +/- 2.6 and 34.0 +/- 9.7 fmol of SP-LI and NKA-LI, respectively, were found in the fraction corresponding to 10-20 min of superfusion. Recovered immunoreactivities decreased to 5.2 +/- 0.3 and 9.3 +/- 1.8 fmol of SP-LI and NKA-LI, respectively, in the fraction corresponding to 110-120 min of superfusion (P less than 0.05). Inhibition of neutral endopeptidase with thiorphan resulted in significantly greater increases in Pao (P less than 0.005) and augmentation of the recovery of SP-LI and NKA-LI (P less than 0.05 and P less than 0.001, respectively). Capsaicin treatment of animals 7-10 days before the removal of their lungs abolished the increase in Pao during superfusion and resulted in a significant decrease in the amount of SP-LI and NKA-LI recovered. Our data confirm that tachykinin release occurs during postmortem bronchoconstriction in guinea pig lungs and, furthermore, that tachykinin degradation by NEP modulates the intensity of this response.

NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea

1995 ◽  
Vol 268 (2) ◽  
pp. L263-L269 ◽  
Author(s):  
P. Baluk ◽  
C. Bertrand ◽  
P. Geppetti ◽  
D. M. McDonald ◽  
J. A. Nadel
Keyword(s):  
Substance P ◽  
Hypertonic Saline ◽  
Receptor Agonist ◽  
Neurogenic Inflammation ◽  
Leukocyte Adhesion ◽  
Neurokinin A ◽  
Plasma Extravasation ◽  
Nk1 Receptor ◽  
Nk1 Receptors ◽  
Plasma Leakage

In neurogenic inflammation, tachykinins trigger the adhesion of neutrophils and eosinophils to leaky venules. The goals of the present study were to determine whether this leukocyte adhesion is mediated by neurokinin type 1 (NK1) receptors and to determine whether the amount of leukocyte adhesion corresponds to the amount of plasma leakage. Anesthetized rats were injected intravenously with substance P, the NK1 receptor agonist [Sar9, Met(O2)11]-substance P, or the NK2 receptor agonist [beta-Ala8]neurokinin A-(4–10). Five minutes later, the adherent neutrophils and eosinophils in blood vessels of the tracheal mucosa were stained histochemically and plasma leakage was quantified, as assessed by the extravasation of Monastral blue. Substance P and the NK1 agonist caused similar amounts of leukocyte adhesion, but the NK2 agonist had no effect. Pretreatment with the NK1 receptor antagonist CP-96,345 (4 mg/kg iv), before challenge with substance P, capsaicin, or aerosol hypertonic saline, reduced the amount of neutrophil adhesion by 56%, 93%, and 57% and reduced the amount of eosinophil adhesion by 70%, 83%, and 65%, respectively. Plasma extravasation was decreased by 89%, 95%, and 94%. The number of adherent neutrophils in the trachea was strongly correlated with the number of adherent eosinophils (r2 = 0.61). The greatest amount of leukocyte adhesion occurred in larger diameter venules than did the maximal amount of Monastral blue leakage. We conclude that NK1 receptors mediate the adhesion of neutrophils and eosinophils as well as the plasma leakage triggered by substance P, capsaicin, or hypertonic saline. This leukocyte adhesion evidently does not occur at exactly the same sites as the plasma leakage.

Neurokinin A but not neurokinin B and substance P induces codeine-resistant coughs in awake guinea-pig

1992 ◽  
Vol 37 ◽  
pp. S154
Author(s):  
K. Takahama ◽  
J. Fuchikami ◽  
Y. Isohama ◽  
H. Kai ◽  
T. Miyata
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Neurokinin A ◽  
Neurokinin B

Substance P-induced histamine release in tracheally perfused guinea pig lungs

1995 ◽  
Vol 78 (4) ◽  
pp. 1234-1241 ◽  
Author(s):  
C. M. Lilly ◽  
A. E. Hall ◽  
I. W. Rodger ◽  
L. Kobzik ◽  
K. J. Haley ◽  
...  
Keyword(s):  
Mast Cells ◽  
Substance P ◽  
Guinea Pig ◽  
Histamine Release ◽  
Receptor Activation ◽  
Neurokinin A ◽  
Histamine Liberation ◽  
Nk1 Antagonist ◽  
Nk2 Receptor ◽  
Receptor Agonists And Antagonists

The capacity of substance P (SP) and endogenously released tachykinins to liberate histamine was examined in isolated tracheally perfused guinea pig lungs. Increasing doses of tracheally injected SP were associated with the recovery of increasing amounts of histamine from lung effluent. The mechanism of SP-induced histamine liberation was explored in studies with neurokinin-(NK) receptor agonists and antagonists. Tracheal injection of either the NK1 agonist [Sar9,Met(O2)11]SP or the NK2 agonist [beta-Ala8]-neurokinin A-(4–10) was associated with a significant increase in histamine recovery from lung effluent. In addition, both the NK1 antagonist CP-99994 and the NK2 antagonist SR-48968 significantly inhibited SP-induced histamine release. These findings support the hypothesis that SP can liberate histamine from guinea pigs lungs by a mechanism that depends predominantly on NK1- and NK2-receptor activation. The liberation of endogenous tachykinins by acute tracheal injection of capsaicin was also associated with augmented histamine recovery, which was inhibited by combined NK1- and NK2-receptor blockade. Tracheal injection of SP was associated with an increase in the percentage of airway mast cells exhibiting histological evidence of degranulation. This study demonstrates that exogenous SP, as well as endogenous tachykinins released from capsaicin-sensitive neurons, can liberate histamine, most likely from airway mast cells, by a mechanism that depends predominantly on the activation of NK1 and NK2 receptors.

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A

1995 ◽  
Vol 73 (7) ◽  
pp. 903-907 ◽  
Author(s):  
M. Qtsuka ◽  
K. Yoshioka ◽  
M. Yanagisawa ◽  
H. Suzuki ◽  
F.-Y. Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Substance P ◽  
Guinea Pig ◽  
Saphenous Nerve ◽  
Ventral Root ◽  
Neonatal Rat ◽  
Neurokinin A ◽  
Receptor Antagonists ◽  
Stimulation Of

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.Key words: substance P, neurokinin A, neurotransmitter, tachykinin antagonist, spinal cord.

Proteolytic Inactivation of Substance P and Neurokinin A in the Longitudinal Muscle Layer of Guinea Pig Small Intestine

2006 ◽  
Vol 47 (3) ◽  
pp. 856-864 ◽  
Author(s):  
R. Nau ◽  
G. Schäfer ◽  
C. F. Deacon ◽  
T. Cole ◽  
D. V. Agoston ◽  
...  
Keyword(s):  
Small Intestine ◽  
Substance P ◽  
Guinea Pig ◽  
Longitudinal Muscle ◽  
Muscle Layer ◽  
Neurokinin A ◽  
Longitudinal Muscle Layer

scholarly journals Presynaptic nicotinic acetylcholine receptors in the myenteric plexus of guinea pig intestine

2000 ◽  
Vol 279 (3) ◽  
pp. G528-G535 ◽  
Author(s):  
David A. Schneider ◽  
James J. Galligan
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Nicotinic Acetylcholine Receptors ◽  
Myenteric Plexus ◽  
Acetylcholine Receptors ◽  
Neurokinin A ◽  
Guinea Pig Ileum ◽  
Nicotinic Acetylcholine ◽  
Neurokinin Receptor ◽  
Electrophysiological Methods

Presynaptic nicotinic acetylcholine receptors (nAChRs) were studied in myenteric plexus preparations from guinea pig ileum using intracellular electrophysiological methods. Microapplication of nicotine (1 mM) caused a biphasic depolarization in all AH neurons ( n = 30) and in 36 of 49 S neurons. Cytisine (1 mM) caused fast depolarizations in S neurons and no response in AH neurons. Mecamylamine (10 μM) blocked all responses caused by nicotine and cytisine. TTX (0.3 μM) blocked slow excitatory synaptic potentials in S and AH neurons but had no effect on fast depolarizations caused by nicotine. Nicotine-induced slow depolarizations were reduced by TTX in two of twelve AH neurons (79% inhibition) and four of nine S neurons (90 ± 12% inhibition). Slow nicotine-induced depolarizations in the remaining neurons were TTX resistant. TTX-resistant slow depolarizations were inhibited after neurokinin receptor 3 desensitization caused by senktide (0.1 μM); senktide desensitization inhibited the slow nicotine-induced depolarization by 81 ± 5% and 63 ± 15% in AH and S neurons, respectively. A low-calcium and high-magnesium solution blocked nicotine-induced slow depolarizations in AH neurons. In conclusion, presynaptic nAChRs mediate the release of substance P and/or neurokinin A to cause slow depolarizations of myenteric neurons.

Sign in / Sign up

Export Citation Format

Share Document