The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs

El-Hashim, Ahmed Z.; Amine, Sanaa A.

doi:10.1016/j.ejphar.2005.02.007

Cited by 44 publications

(34 citation statements)

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“…All of 50 representative control animals and 69 of 84 animals undergoing any of the interventions described above had augmented breaths during the citric acid challenge. The majority (Ͼ80%) of animals studied produced multiple (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) augmented breaths during the citric acid challenges. Severing either the RLNs or SLNs, or TTX pretreatment decreased the number of augmented breaths induced by citric acid challenge (8 of the 11 animals in these treatment groups sighed Յ1 time and six of these eleven did not sigh at all during the citric acid challenges).…”

Section: Resultsmentioning

confidence: 99%

“…Not surprisingly, therefore, citric acid-induced coughing was unaffected by pretreatment with atropine, the ␤-agonists albuterol and isoproterenol, the cyclooxygenase inhibitor indomethacin, the bradykinin B2 receptor antagonist FR-173657, the combination of pyrilamine and ICI-198615 (histamine and cysteinyl-leukotriene receptor antagonists, respectively), or depletion of extracellular Ca 2ϩ . This reveals an additional distinction between airway C fibers and the cough receptors, because airway C fibers can be directly activated by some autacoids [e.g., 5-HT, adenosine, bradykinin, ATP, anandamide, 15-HETE (23,25,37,56)] and sensitized by others [e.g., bradykinin, histamine, PGE2, adrenaline (8,13,17,19,30,36)]. Rather, the effects of acid on the cough receptors appeared to be direct.…”

Section: Fig 7 Lowering the CLmentioning

confidence: 99%

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Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs

Canning

Farmer

Mori

2006

American Journal of Physiology-Regulatory, Integrative and Comp

103

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ments carried out in conscious guinea pigs suggest that citric acidevoked coughing is partly mediated by transient receptor potential vanilloid type 1 (TRPV1) receptor-dependent activation of tachykinin-containing, capsaicin-sensitive C fibers. In vitro electrophysiological analyses indicate, however, that acid also activates capsaicinsensitive and -insensitive vagal afferent nerves by a TRPV1-independent mechanism, and studies in anesthetized guinea pigs show that coughing evoked by acid is mediated by activation of capsaicininsensitive vagal afferent nerves. In the present study, we have characterized the mechanisms of citric acid-evoked coughing in anesthetized guinea pigs. Drugs were administered directly to the Krebs buffer perfusing the extrathoracic trachea. Citric acid was applied topically to the tracheal mucosa, directly into the tracheal perfusate in increasing concentrations and at 1-min intervals. Citric acid dose dependently evoked coughing in anesthetized guinea pigs. This was mimicked by hydrochloric acid but not by sodium citrate. The coughing evoked by acid was nearly or completely abolished by TTX or by cutting the recurrent laryngeal nerves. Perfusing the trachea with a low Cl Ϫ buffer potentiated the acid-induced cough reflex. In contrast, prior capsaicin desensitization, 10 M capsazepine, Ca 2ϩ -free perfusate, 0.1 M iberiotoxin, 1 M atropine, 10 M isoproterenol, 10 M albuterol, 3 M indomethacin, 0.1 M HOE-140, a combination of neurokinin 1 (NK1; CP-99994), NK2 (SR-48968), and NK3 (SB-223412) receptor antagonists (0.1 M each), a combination of histamine H 1 (3 M pyrilamine) and cysLT1 (1 M ICI-198615) receptor antagonists, superior laryngeal nerve transection, or epithelium removal did not inhibit citric acid-evoked coughing. These and other data indicate that citric acid-evoked coughing in anesthetized guinea pigs is mediated by direct activation of capsaicin-insensitive vagal afferent nerves, perhaps through sequential activation of acid-sensing ion channels and chloride channels. TRPV1 ; capsaicin; rapidly adapting receptor CITRIC ACID AND TARTARIC ACID are used routinely in clinical and preclinical studies of the cough reflex (15,27,35). In conscious guinea pigs, citric acid-evoked coughing is inhibited by the capsaicin receptor transient receptor potential vanilloid type 1 (TRPV1) antagonists capsazepine and iodo-resiniferatoxin or the TRPV1 channel blocker Ruthenium Red, and can also be inhibited by neurokinin 1 (NK 1 ), NK 2 , and/or NK 3 receptor antagonists (1,2,7,18,34,54,55). The acid-evoked coughing is mimicked by inhalation of the TRPV1 receptor agonists capsaicin, resiniferatoxin, and anandamide in both animals and human subjects, and prior capsaicin desensitization abolishes citric acid-evoked coughing in awake guinea pigs (10,25,35,50). Because the only tachykinin-containing nerves innervating the airways of normal, uninflamed guinea pigs are capsaicinsensitive C fibers (21, 32 49, 56), these data provide overwhelming evidence that acid-evoked coughing in conscious guinea pi...

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Section: Resultsmentioning

confidence: 99%

Section: Fig 7 Lowering the CLmentioning

confidence: 99%

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs

Canning

Farmer

Mori

2006

American Journal of Physiology-Regulatory, Integrative and Comp

103

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“…Indeed, it was postulated that elevated SP in nasal secretions defines a distinct population of patients with chronic cough, those with "upper airway cough syndrome" (Lim et al, 2011). The interpretation of these observations is, however, not straightforward since inhaled SP does not provoke cough in the guinea pig (El-Hashim and Amine, 2005), nor do tachykinin NK1R (the receptor SP) antagonists relieve spontaneous coughing in men (Joos et al, 1996). Thus far, elevated SP appears to be marker of overactive sensory nerves in the respiratory tract, rather than a diseasecausing substance.…”

Section: B Transient Receptor Potential Channels Inmentioning

confidence: 97%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

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“…The sensitization of cough apparent when comparing the responses to bradykininevoked cough with or without preceding subthreshold challenge doses has not been previously described. However, a sensitizing effect of subthreshold doses of bradykinin on subsequently evoked cough responses has been noted (Fox et al, 1996;El-Hashim and Amine, 2005;Mazzone et al, 2005). These sensitizing effects may be both central nervous system and NK 1 receptor dependent (Joad et al, 2004;Mazzone et al, 2005;Canning and Mori, 2011;Cinelli et al, 2015) or could depend on local actions of eicosanoids released from structural cells following bradykinin B 2 receptor activation (Salari and Chan-Yeung, 1989;Arakawa et al, 1992;Gatti et al, 2006;Petho and Reeh, 2012).…”

Section: Treatmentmentioning

confidence: 99%

Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs

Hewitt

Adams

Mazzone

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B 2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B 2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N G

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The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs

Cited by 44 publications

References 44 publications

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs

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