Tachykinin receptors in guinea-pig airways: characterization using selective ligands

1995 ◽  
Vol 73 (7) ◽  
pp. 915-922 ◽  
Author(s):  
Elizabeth Burcher ◽  
Xiang-Ping Zeng ◽  
John Strigas ◽  
Dominic P. Geraghty ◽  
Solange Lavielle
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Radioligand Binding ◽  
Neurokinin A ◽  
Tachykinin Receptors ◽  
Tachykinin Receptor ◽  
High Affinity ◽  
Selective Ligands ◽  
Dose Dependent ◽  
Potency Order

Tachykinin receptors in guinea-pig airways were examined using radioligand binding techniques in lung homogenates, and using isolated bronchial segments. Binding of the NK1 selective radioligand 125I-labelled Bolton–Hunter [Sar9,Met(O2)11]substance P ([125I]BHSarSP) was saturable and of high affinity (KD, 0.26 nM). The rank potency order of competitors for [125I]BHSarSP binding was [Pro9]SP > CP 96345 [Formula: see text] septide > [pGlu6]SP(6–11) > RP 67580 ≥ [DPro9, [Formula: see text],Trp11]SP > [DPro9,[Formula: see text],Trp11]physalaemin ≥ GR 82334 ≥ 127I Bolton–Hunter neurokinin A (BHNKA). Septide had higher affinity than expected, and it was the only ligand to bind to two sites. Agonists interacting with NK2 receptors were more potent contractile agents than NK1 receptor agonists. Responses to BHNKA (pD2 8.4) were antagonized by MDL 29913 and MEN 10207, with pKB values 6.42 and 6.79, and also by SR 48968 and GR 94800, although this was not dose dependent. This agonist was also weakly inhibited by CP 96345 and RP 67580. These data demonstrate that BHNKA can interact with both NK1 and NK2 receptors. There was no relationship between the binding affinity of NK1 ligands in lung homogenates, with GR 82334 being notably weak, and their agonist or antagonist potency in bronchial smooth muscle.Key words: tachykinin receptor, radioligand binding, septide, guinea-pig bronchus, 127I Bolton–Hunter neurokinin A.

Tachykinin receptors in smooth muscles: A study with agonists (substance P, neurokinin A) and antagonists

1985 ◽  
Vol 118 (1-2) ◽  
pp. 25-36 ◽  
Author(s):  
Jacques Mizrahi ◽  
Stéphane Dion ◽  
Pedro D'Orléans-Juste ◽  
Emanuel Escher ◽  
Guy Drapeau ◽  
...  
Keyword(s):  
Substance P ◽  
Smooth Muscles ◽  
Neurokinin A ◽  
Tachykinin 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.

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Neurokinin A ◽  
Dependent Manner ◽  
C Fiber ◽  
Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

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

Characterization of the effects of neurokinins on canine antral muscle

1988 ◽  
Vol 255 (6) ◽  
pp. G779-G786
Author(s):  
C. B. Koelbel ◽  
E. A. Mayer ◽  
G. van Deventer ◽  
W. J. Snape ◽  
A. Patel
Keyword(s):  
Substance P ◽  
Mechanical Response ◽  
Longitudinal Muscle ◽  
Rank Order ◽  
Circular Muscle ◽  
Neurokinin A ◽  
Inotropic Response ◽  
Chronotropic Response ◽  
Natural Ligand ◽  
Dose Dependent

The excitation of longitudinal antral muscle by substance P (SP) involves both a myogenic and a cholinergic effect. To examine if these responses are mediated by different neurokinin receptors, we studied the mechanical response and the release of [3H]acetylcholine from antral muscle strips in response to SP, substance P methylester (SPME), neurokinin A (NKA), neurokinin B (NKB), and several non-mammalian tachykinins. All peptides studied showed a dose-dependent inotropic and chronotropic effect on spontaneous phasic contractions. This ionotropic effect in longitudinal muscle was partially atropine sensitive for SPME, SP, and NKB but not for NKA, whereas neither atropine nor tetrodotoxin had an effect in circular muscle. In longitudinal muscle, all three neurokinins were equipotent. In longitudinal muscle treated with atropine and in circular muscle, the rank order of potency for the inotropic response was NKA greater than NKB greater than SP greater than SPME. For the chronotropic response the rank order was SPME, SP greater than NKA greater than NKB. NKA, NKB, and SP caused a dose-dependent, tetrodotoxin-sensitive increase in [3H]acetylcholine release from strips preincubated with [3H]choline. NKA was significantly more potent to release [3H]acetylcholine than either NKB or SP. The stimulated release was inhibited by [D-Ala2,D-Met5]methionine enkephalinamide and the SP antagonist, spantide. These results are consistent with the hypothesis that NKA is the natural ligand mediating the myogenic inotropic response in both muscle layers and the cholinergic response in longitudinal muscle.

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
Sign in / Sign up

Export Citation Format

Share Document