Thesis

The cough reflex : properties of rapidly adapting stretch receptors in relation to inhaled tussigenic stimuli and some potential anti-tussive/anti-asthmatic agents

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Awarding institution
  • University of Strathclyde
Date of award
  • 1994
Thesis identifier
  • T7912
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Department, School or Faculty
Abstract
  • Activation of airway afferent sensory nerve endings evokes numerous airway reflexes including cough. However, the distribution and type of nerve endings involved in evoking individual reflexes are unclear. The primary purpose of the present study was to examine the distribution of airway afferent sensory nerve endings in man responsive to "selective" C-fibre stimulants used to evoke cough and to establish the degree of selectivity of these agents on airway afferent sensory nerve endings in anaesthetized cats. A secondary purpose was to investigate if a group of these sensory nerve endings, i.e. rapidly adapting stretch receptors (RARs) are involved in the anti-tussive/anti-bronchoconstrictor action of the loop diuretic, frusemide. A third purpose was to ascertain if neurotransmitters, which cause hyperalgesia, are important in the development of airway hyperreactivity through a sensory neuronal mechanism. Inhaled capsaicin and prostaglandin E2 evoked coughing in human subjects; the central airways more responsive to prostaglandin E2 and the peripheral airways more responsive to capsaicin. In anaesthetized cats, inhaled capsaicin was not selective for C-fibres, since a proportion of RARs were activated independently of changes in pulmonary mechanics. Furthermore, PGE2 caused a dose-dependent increase in RAR discharge and a dose-related bronchoconstriction, possibly through activation of EP2 receptors. Frusemide had no effect on the spontaneous activity of RARs in anaesthetized cats whereas 443C81, the peripherally-acting p-opioid agonist, significantly inhibited the spontaneous activity of RARs. The neurotransmitter glutamate which causes hyperalgesia had no effect on airway tone or the spontaneous discharge of RARs in cats. Although lamotrigine, a glutamate release inhibitor, was anti-bronchoconstrictor at high doses, it is unlikely to have any therapeutic potential in asthma. Capsaicin and PGE2 are not, as previously thought, selective for either C-fibre endings or RARs. Furthermore, RARs may be the sensory nerve endings primarily responsible for evoking the cough reflex, and represent a potential therapeutic target for inhibiting this reflex response.
Advisor / supervisor
  • Adcock, John
Resource Type
DOI
EThOS ID
  • uk.bl.ethos.881502

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