Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs

1995 ◽  
Vol 79 (4) ◽  
pp. 1082-1087 ◽  
Author(s):  
U. G. Lalloo ◽  
A. J. Fox ◽  
M. G. Belvisi ◽  
K. F. Chung ◽  
P. J. Barnes
Keyword(s):  
Citric Acid ◽  
Hypertonic Saline ◽  
Guinea Pigs ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Sensory Nerves ◽  
Cough Reflex ◽  
Acidic Solutions ◽  
Nasal Irritation ◽  
Cough Response

Acidic solutions mimick many of the effects of capsaicin (Cap), including pain, bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the use of the Cap antagonist capsazepine suggests that in some cases protons act at the Cap receptor. In the present study, we have investigated whether cough evoked by Cap and citric acid (CA) is mediated specifically via the Cap receptor on airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-, and hypertonic saline-induced cough and also on CA-induced nasal irritation in awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges with Cap for 5 min and CA for 10 min. Control animals were pretreated with vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P < 0.01). There was no effect, however, of lower concentrations of capsazepine (5 and 10 microM) against Cap-evoked cough. At a concentration of 100 microM, capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to 0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This inhibitory effect of capsazepine did not appear to reflect a nonspecific suppression of the cough reflex, since cough evoked by exposure to hypertonic (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100 microM). These data show that capsazepine is a specific inhibitor of Cap- and CA-induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke cough and nasal irritation by an action at the Cap receptor, either directly or through the release of an intermediate agent.

scholarly journals Opposing effects of bronchopulmonary C-fiber subtypes on cough in guinea pigs

2018 ◽  
Vol 314 (3) ◽  
pp. R489-R498 ◽  
Author(s):  
Yang-Ling Chou ◽  
Nanako Mori ◽  
Brendan J. Canning
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Respiratory Pattern ◽  
Tracheal Mucosa ◽  
Cough Reflex ◽  
C Fibers ◽  
Selective Agonist ◽  
Nodose Ganglia ◽  
C Fiber ◽  
Opposing Effects

We have addressed the hypothesis that the opposing effects of bronchopulmonary C-fiber activation on cough are attributable to the activation of C-fiber subtypes. Coughing was evoked in anesthetized guinea pigs by citric acid (0.001–2 M) applied topically in 100-µl aliquots to the tracheal mucosa. In control preparations, citric acid evoked 10 ± 1 coughs cumulatively. Selective activation of the pulmonary C fibers arising from the nodose ganglia with either aerosols or continuous intravenous infusion of adenosine or the 5-HT3 receptor-selective agonist 2-methyl-5-HT nearly abolished coughing evoked subsequently by topical citric acid challenge. Delivering adenosine or 2-methyl-5-HT directly to the tracheal mucosa (where few if any nodose C fibers terminate) was without effect on citric acid-evoked cough. These actions of pulmonary administration of adenosine and 2-methyl-5-HT were accompanied by an increase in respiratory rate, but it is unlikely that the change in respiratory pattern caused the decrease in coughing, as the rapidly adapting receptor stimulant histamine also produced a marked tachypnea but was without effect on cough. In awake guinea pigs, adenosine failed to evoke coughing but reduced coughing induced by the nonselective C-fiber stimulant capsaicin. We conclude that bronchopulmonary C-fiber subtypes in guinea pigs have opposing effects on cough, with airway C fibers arising from the jugular ganglia initiating and/or sensitizing the cough reflex and the intrapulmonary C fibers arising from the nodose ganglia actively inhibiting cough upon activation.

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 Differential effects of airway afferent nerve subtypes on cough and respiration in anesthetized guinea pigs

2008 ◽  
Vol 295 (5) ◽  
pp. R1572-R1584 ◽  
Author(s):  
Yang-Ling Chou ◽  
Mark D. Scarupa ◽  
Nanako Mori ◽  
Brendan J. Canning
Keyword(s):  
Citric Acid ◽  
Hypertonic Saline ◽  
Guinea Pigs ◽  
Afferent Nerve ◽  
Vagal Afferents ◽  
C Fibers ◽  
Afferent Nerves ◽  
Nodose Ganglia ◽  
Opposing Effects ◽  
Respiratory Reflexes

The hypothesis that respiratory reflexes, such as cough, reflect the net and often opposing effects of activation of multiple afferent nerve subpopulations throughout the airways was evaluated. Laryngeal and tracheal mucosal challenge with either citric acid or mechanical probing reliably evoked coughing in anesthetized guinea pigs. No other stimulus reliably evoked coughing in these animals, regardless of route of administration and despite some profound effects on respiration. Selectively activating vagal C-fibers arising from the nodose ganglia with either adenosine or 2-methyl-5-HT evoked only tachypnea. Selectively activating vagal afferents arising from the jugular ganglia induced respiratory slowing and apnea. Nasal afferent nerve activation by capsaicin, citric acid, hypertonic saline, or histamine evoked only respiratory slowing. Histamine, which activates intrapulmonary rapidly adapting receptors but not airway or lung C-fibers or tracheal bronchial cough receptors induced bronchospasm and tachypnea, but no coughing. The results indicate that the reflexes initiated by stimuli thought to be selective for some afferent nerve subtypes will likely depend on the net and potentially opposing effects of multiple afferent nerve subpopulations throughout the airways. The data also provide further evidence that the afferent nerves regulating cough in anesthetized guinea pigs are distinct from either C-fibers or intrapulmonary rapidly adapting receptors.

Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans

1994 ◽  
Vol 76 (3) ◽  
pp. 1082-1087 ◽  
Author(s):  
F. O′Connell ◽  
V. E. Thomas ◽  
R. W. Fuller ◽  
N. B. Pride ◽  
J. A. Karlsson
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Healthy Human ◽  
Oral Clonidine ◽  
Healthy Humans ◽  
Human Volunteers ◽  
Dependent Inhibition ◽  
Time To Onset

We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10–1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2-receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species.

scholarly journals Female Guinea Pig Model for Cough Studies and Its Response to Most Common Tussive Substances

2020 ◽  
pp. S171-S179
Author(s):  
M. Sterusky ◽  
J. Plevkova ◽  
M. Grendar ◽  
T. Buday
Keyword(s):  
Guinea Pigs ◽  
Allyl Isothiocyanate ◽  
Laboratory Animals ◽  
Laboratory Research ◽  
Cough Reflex ◽  
Pooled Data ◽  
Cough Response ◽  
Multiple Challenges ◽  
Guinea Pig Model

Laboratory research of cough reflex utilizes almost exclusively male guinea pigs – a practice that represents a significant obstacle in the successful translation of results into clinical practice. Chronic hypersensitivity cough syndrome affects mostly postmenopausal women and it represents significant decrease in patient’s quality of life. No cause for such exaggerated cough can be found, therefore this condition cannot be treated appropriately. One of the reasons leading to the lack of relevant data about mechanisms responsible for hypersensitivity of cough related pathways is nowadays widely discussed gender bias, which is present in nearly all branches of biomedical research. Since gender differences in cough reflex physiology do exist in humans, it would be reasonable to study cough-related phenomena on both sexes of laboratory animals. In this study, we focused on detailed characterization of cough response of female guinea pigs to aerosols of commonly used tussive agents (capsaicin, distilled water, allyl isothiocyanate, cinnamaldehyde, citric acid). In pooled data from multiple challenges we found no statistical difference in number of cough and cough latency between sexes. Based on our results we conclude that the utilization of female guinea pigs model does not lead to messy data and can be used in basic cough research.

scholarly journals Cineole, Thymol and Camphor Nasal Challenges and their Effect on Nasal Symptoms and Cough in an Animal Model

2013 ◽  
Vol 13 (2) ◽  
pp. 5-13 ◽  
Author(s):  
S Gavliakova ◽  
T Dolak ◽  
H Licha ◽  
S Krizova ◽  
J Plevkova
Keyword(s):  
Animal Model ◽  
Citric Acid ◽  
Statistical Significance ◽  
Intraperitoneal Administration ◽  
Sensory Nerves ◽  
Skin Tests ◽  
Cough Reflex ◽  
Nasal Symptoms ◽  
Nasal Application ◽  
Pre Treatment

Abstract Inhalation of aromatic vapours suppressed coughing induced by citric acid (CA) in naive animals. No data are available about their effects in an animal model with primarily up-regulated cough reflex. New data indicate that aromatic vapours suppress cough via effect on nasal sensory nerves. The aim of our study was to ascertain the efficacy of nasal application of 1,8-cineole, thymol and camphor on nasal symptoms and CA induced cough in validated model of up-regulated cough reflex. Guinea pigs (n=13) were sensitized by intraperitoneal administration of ovalbumin (OVA) and sensitization was confirmed 21 days later by skin tests. Sensitized animals were repeatedly challenged with nasal OVA to induce rhinitis, and further experiments (cough challenges) were performed during the early phase of allergic inflammation. Cough was induced by CA in plethysmograph for 10 minutes after nasal pre-treatment with aromatic substances (10-3M) in rhinitis model. Cough was recognized from record of sudden airflow changes interrupting breathing pattern and cough sound. Final count of coughs was established by blind analysis using SonicVisualiser Software. Dose responses curves, total cough count and cough latency were analyzed. Repeated intranasal challenge with OVA induces progressively worsening symptoms, and cough induced by CA during acute phase of allergic rhinitis was enhanced. Nasal pre-treatment with 1,8-cineole, thymol and camphor did not prevent onset of nasal symptoms, and the magnitude of symptoms was comparable to those without pretreatment. Camphor had the most potent antitussive effects (number of coughs 25±3 vs. 7±2, p<0.05) followed by thymol (number of coughs 25±3 vs. 14±2, p<0.05). The data for nasal 1,8-cineole challenge did not reach statistical significance. Cough latency followed this trend. Although the magnitude of nasal symptoms is not influenced, the effect on cough is in case of camphor and thymol significant. Our data showed that nasal application of aromatic substances suppress citric acid induced cough in animals with up-regulated cough reflex.

Suppressive effect of pectic polysaccharides from Cucurbita pepo L. var. Styriaca on citric acid-induced cough reflex in guinea pigs

Fitoterapia ◽  
2011 ◽  
Vol 82 (3) ◽  
pp. 357-364 ◽  
Author(s):  
Gabriela Nosáľová ◽  
Ľubica Prisenžňáková ◽  
Zuzana Košťálová ◽  
Anna Ebringerová ◽  
Zdenka Hromádková
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Cucurbita Pepo ◽  
Suppressive Effect ◽  
Pectic Polysaccharides ◽  
Cough Reflex

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

scholarly journals Metabolism of Citric Acid in Scorbutic Guinea Pigs

1960 ◽  
Vol 235 (4) ◽  
pp. 902-905
Author(s):  
Sachchidananda Banerjee ◽  
Haobam Devendra Singh
Keyword(s):  
Citric Acid ◽  
Guinea Pigs
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