Involvement of neurogenic inflammation in antigen-induced bronchoconstriction in guinea pigs

1993 ◽  
Vol 265 (5) ◽  
pp. L507-L511 ◽  
Author(s):  
C. Bertrand ◽  
P. Geppetti ◽  
P. D. Graf ◽  
A. Foresi ◽  
J. A. Nadel
Keyword(s):  
Guinea Pigs ◽  
Neurogenic Inflammation ◽  
Neutral Endopeptidase ◽  
Receptor Activation ◽  
Sensory Nerves ◽  
Pulmonary Resistance ◽  
Receptor Antagonists ◽  
Tachykinin Receptor ◽  
Nk2 Receptor

The role of tachykinins released from sensory nerves in bronchoconstriction induced by antigen was studied in sensitized guinea pigs anesthetized with pentobarbital sodium and pretreated with atropine. The combination of NK2 (SR-48968) and NK1 (CP-96,345) tachykinin-receptor antagonists abolished the increase in total pulmonary resistance (RL) evoked by intravenous capsaicin but did not affect the response evoked by intravenous histamine. A small dose of aerosolized ovalbumin (OVA, 0.1%) produced a small increase in RL that was further increased and markedly prolonged by the neutral endopeptidase (NEP) inhibitor phosphoramidon; this bronchoconstrictor effect of OVA was markedly reduced by the NK2-receptor antagonist and was abolished by the combination of the NK1 and NK2-receptor antagonists together. When a larger dose of OVA (0.5%) was used, a maximal bronchoconstrictor response was obtained. Phosphoramidon did not potentiate this response significantly. The combination of NK1- and NK2-receptor antagonists blunted the response at 5 min only slightly but markedly attenuated the later (10–20 min) response. These results show that tachykinins released from sensory nerves play a significant role in antigen-induced bronchoconstriction in guinea pigs. This effect is exaggerated when the normal modulation of neuropeptides by NEP is inhibited and is mediated predominantly by NK2-receptor activation, with a smaller contribution by NK1 receptors.

New aspects on the role of kinins in neurogenic inflammation

1995 ◽  
Vol 73 (7) ◽  
pp. 843-847 ◽  
Author(s):  
Pierangelo Geppetti ◽  
Claude Bertrand ◽  
Fabio M. L. Ricciardolo ◽  
Jay A. Nadei
Keyword(s):  
Guinea Pigs ◽  
Neurogenic Inflammation ◽  
Tissue Injury ◽  
Inhibitory Effect ◽  
Cellular Systems ◽  
Sensory Nerves ◽  
Antigen Challenge ◽  
Plasma Extravasation ◽  
Receptor Antagonists ◽  
Kinin Receptor

The inflammatory response to injury consists of the activation of several protective mechanisms involving different cellular systems. Among the mechanisms and systems that exert their effects rapidly, peptide transmitters released from peripheral endings of primary sensory neurons (evoking neurogenic inflammation) play a major role in the response to tissue injury. Noxious stimuli may directly activate sensory nerves to release proinflammatory neuropeptides. More recently, evidence has accumulated suggesting that indirect mechanisms leading to sensory neuropeptide release are also activated in relevant models of pathophysiological conditions. Tachykinin NK1 and NK2 receptor antagonists reduced the plasma extravasation in the trachea and nasal mucosa and the bronchoconstriction caused by antigen challenge in sensitized guinea-pigs. Blockade of kinin B2 receptors with the selective antagonist HOE-140 had a similar inhibitory effect. The magnitude of the inhibition observed with the kinin receptor antagonist alone was similar to that caused by a combination a tachykinin and kinin receptor antagonists. This suggests activation of a common final pathway by these two groups of mediators. Pharmacological and biochemical evidence suggests that in the airways of sensitized guinea-pigs, kinins released by the anaphylactic reaction stimulate the release of tachykinins from sensory nerves, thus contributing to their proinflammatory action.Key words: kinins, tachykinins, neurogenic inflammation, antigen challenge, airways, nitric oxide.

scholarly journals The Role of Tachykinin Receptor Antagonists on Hyperpnea-induced Bronchoconstriction in Guinea Pigs

2008 ◽  
Vol 67 (6) ◽  
pp. 339-345
Author(s):  
Kaori Tsuda ◽  
Toru Majima ◽  
Reiko Ito ◽  
Tomohiro Hattori ◽  
Tsuneto Akashiba
Keyword(s):  
Guinea Pigs ◽  
Receptor Antagonists ◽  
Tachykinin Receptor

scholarly journals Role of neutral endopeptidase in endotoxin-induced bronchial hyperresponsiveness to substance P in guinea pigs

1998 ◽  
Vol 47 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Shigenori Iwamae ◽  
Hideo Tsukagoshi ◽  
Takeshi Hisada ◽  
Daisuke Uno ◽  
Masatomo Mori
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Bronchial Hyperresponsiveness ◽  
Neutral Endopeptidase

Airway neutral endopeptidase-like enzyme modulates tachykinin-induced bronchoconstriction in vivo

1988 ◽  
Vol 65 (6) ◽  
pp. 2585-2591 ◽  
Author(s):  
D. J. Dusser ◽  
E. Umeno ◽  
P. D. Graf ◽  
T. Djokic ◽  
D. B. Borson ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Guinea Pigs ◽  
Vagus Nerve Stimulation ◽  
Neutral Endopeptidase ◽  
Base Line ◽  
Pulmonary Resistance

To determine whether neutral endopeptidase (NEP), also called enkephalinase (EC 3.4.24.11), modulates the effects of exogenous and endogenous tachykinins in vivo, we studied the effects of aerosolized phosphoramidon, a specific NEP inhibitor, on the responses to aerosolized substance P (SP) and on the atropine-resistant response to vagus nerve stimulation (10 V, 5 ms for 20 s) in guinea pigs. SP alone (10(-7) to 10(-4) M; each concentration, 7 breaths) caused no change in total pulmonary resistance (RL, P greater than 0.5). Phosphoramidon (10(-4) M, 90 breaths) caused no change either in base-line RL (P greater than 0.5) or in the response to aerosolized acetylcholine (P greater than 0.5). However, in the presence of phosphoramidon, SP (7 breaths) produced a concentration-dependent increase in RL at concentrations greater than or equal to 10(-5) M (P less than 0.001). Phosphoramidon (10(-7) to 10(-4) M; each concentration, 90 breaths) induced a concentration-dependent potentiation of SP-induced bronchoconstriction (10(-4) M, 7 breaths; P less than 0.01). Vagus nerve stimulation (0.5-3 Hz), in the presence of atropine, induced a frequency-dependent increase in RL (P less than 0.001). Phosphoramidon potentiated the atropine-resistant responses to vagus nerve stimulation (P less than 0.001) at frequencies greater than 0.5 Hz. The tachykinin antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P abolished the effects of phosphoramidon on the atropine-resistant response to vagus nerve stimulation (2 Hz, P less than 0.005). NEP-like activity in tracheal homogenates of guinea pig was inhibited by phosphoramidon with a concentration producing 50% inhibition of 5.3 +/- 0.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects of nonpeptide tachykinin receptor antagonists on experimental gut inflammation in rats and guinea-pigs

Life Sciences ◽  
1998 ◽  
Vol 63 (4) ◽  
pp. 293-304 ◽  
Author(s):  
Ludmilla Mazelin ◽  
Vassilia Theodorou ◽  
Jean More ◽  
Xavier Emonds-Alt ◽  
Jean Fioramonti ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Receptor Antagonists ◽  
Gut Inflammation ◽  
Tachykinin Receptor

scholarly journals Characterization of cough evoked by inhaled treprostinil and treprostinil palmitil

2020 ◽  
pp. 00592-2020 ◽  
Author(s):  
Richard W. Chapman ◽  
Michel R. Corboz ◽  
Carlos Fernandez ◽  
Eugene Sullivan ◽  
Andy Stautberg ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Aqueous Suspension ◽  
Sensory Nerves ◽  
Receptor Subtype ◽  
Cyclooxygenase Inhibitor ◽  
Dry Powder ◽  
Receptor Antagonists ◽  
C Fibers ◽  
Suspension Formulation ◽  
Inhaled Prostacyclin

Cough is induced by inhaled prostacyclin analogs including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved with TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS).Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously.In guinea pigs, cough with inhaled TRE (1.23 µg·kg−1) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg) to induce cough. TRE cough was blocked with IP and tachykinin NK1 receptor antagonists but not with EP1, EP2, EP3, DP1 or bradykinin B2 antagonists or a cyclooxygenase inhibitor. TRE administered to the isolated larynx or intravenously in rats produced no apnea or swallowing, whereas citric acid, capsaicin and hypertonic saline had significant effects.The mechanisms inducing cough with inhaled TRE likely involves the activation of prostanoid IP receptors on jugular C-fibers in the tracheobronchial airways. Cough induced by inhaled dry powder and nebulised formulations of TP occurs at higher inhaled doses than TRE, presumably due to the slow, sustained release of TRE from the prodrug resulting in lower concentrations of TRE at the airway sensory nerves.

Neutral endopeptidase inhibitor potentiates allergic bronchoconstriction in guinea pigs in vivo

1993 ◽  
Vol 75 (1) ◽  
pp. 185-190 ◽  
Author(s):  
O. Kawano ◽  
H. Kohrogi ◽  
T. Yamaguchi ◽  
S. Araki ◽  
M. Ando
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Transpulmonary Pressure ◽  
Neutral Endopeptidase ◽  
Allergic Response ◽  
Pulmonary Resistance ◽  
Parasympathetic Nerve ◽  
Mechanically Ventilated ◽  
Airway Response

To determine whether endogenous tachykinins are released in allergic airway response to contribute to bronchoconstriction and whether neutral endopeptidase (NEP), which effectively cleaves tachykinins, modulates that bronchoconstriction, we studied the effects of the NEP inhibitor phosphoramidon on bronchoconstriction induced by allergic response in anesthetized guinea pigs. We mechanically ventilated the guinea pigs sensitized with ovalbumin (OVA) in a bodyplethysmograph and measured the pulmonary resistance (RL). We exposed the sensitized guinea pigs to doubling concentrations of OVA aerosols from 2(-5)% (wt/vol) until the transpulmonary pressure increased more than twofold from the baseline. After the final exposure, we exposed them to phosphoramidon (10(-4) M) or its vehicle. Phosphoramidon significantly potentiated the increased RL induced by OVA challenge. Phosphoramidon also significantly potentiated the increased RL in the guinea pigs treated with atropine, but the potentiation was significantly reduced. In contrast, phosphoramidon failed to potentiate the increased RL induced by OVA in guinea pigs pretreated with capsaicin. These results suggest that 1) endogenous tachykinin-like substances are released in allergic airway response and that 2) when endogenous NEP is inhibited in the guinea pig airways in vivo, the substances contribute to bronchoconstriction by partly activating the parasympathetic nerve.

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