Sensory receptor activation by mediators of defense reflexes in guinea-pig lungs
Introduction
Activation of sensory receptors in the airways by exogenous and endogenous mediators initiates both central and local defense reflexes (Barnes et al., 1991). Defense reflexes increase airway smooth muscle tone and secretions as well as induce vasodilation and plasma exudation, particularly in asthma. Defense reflexes often are attributed to activation of RARs or the so called `irritant' receptors (Karlsson et al., 1988). Certain mediators released during mechanisms of lung defense are reported to directly activate RARs, these include histamine (Mills et al., 1969, Vidruk et al., 1977), which is released during mast cell degranulation and bradykinin (Hargreaves et al., 1993), which is formed during kallikrein activation.
Recent attention has focused on the role of sensory C-fibers in pulmonary defense reflexes. C-fibers not only evoke centrally- mediated reflexes, which influence pulmonary and cardiovascular function but also mediate the local or `axon' reflex in which neuropeptides are released (Saria et al., 1988). Neuropeptides released from C-fibers may include neurokinin A, substance P and calcitonin gene related peptide.
Whether both categories of sensory receptors mediate defense reflexes is unresolved. Moreover the specific endogenous and exogenous mediators that act directly on RARs or C-fibers has been controversial. Histamine was reported to directly activate RARs in cats and dogs (Mills et al., 1969, Vidruk et al., 1977) and C-fibers in dogs (Coleridge and Coleridge, 1977). On the other hand histamine was reported to act only indirectly on RARs in dogs, guinea pigs and rats (Coleridge and Coleridge, 1977, Bergren and Sampson, 1982, Bergren and Peterson, 1993) and to have no effect on C-fibers in guinea pigs in vitro (Fox et al., 1993). Both direct (Hargreaves et al., 1993) and indirect (Kaufman et al., 1980) activation of RARs by bradykinin has been reported. Bradykinin directly activates bronchial C-fibers in dogs (Kaufman et al., 1980) and guinea pig tracheal and main stem bronchi C-fibers in vitro (Fox et al., 1993). However, both histamine and bradykinin are reported to induce neuropeptide release from C-fibers via the `axon' reflex (Saria et al., 1988) which implies direct C-fiber activation.
The purpose of the present study was to determine whether mediators believed to induce defense reflexes, i.e. histamine, bradykinin and capsaicin, activate RARs and C-fibers, and if so whether the activation is direct or indirect. It is likely that only directly stimulated fibers actually initiate defense reflexes.
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Methods
Guinea pigs of either sex (772±13 g) were anesthetized with sodium pentobarbital (35–50 mg/kg i.p., Flecknell, 1987). Surgical anesthesia was maintained throughout the experiment with supplemental injections of one-quarter of the original dose. The level of anesthesia was determined by testing spinal, cardiovascular and corneal reflexes. An anterior, mid-line incision was made in the neck. The trachea was cannulated three to four cartilaginous rings below the larynx. The cannula extended into
Rapidly adapting receptors
The distribution of 74 RARs was 11% in the apex, 36% in the middle and 54% in the base of the lungs. The average conduction velocity of 74 RARs was 21.6±1.3 m/sec, the slowest being 6 m/sec. Base level activity of the RARs was irregular with frequencies ranging from 0 to 1.1 impulses per sec (imp/sec).
Histamine aerosol (9×10−5 M, 30–60 sec) increased PTr and RAR NA simultaneously (Fig. 1). RAR NA displayed respiratory modulation in nearly every case. Heart rate and systemic blood pressure were
Discussion
Central and local defense reflexes can induce bronchoconstriction (Barnes et al., 1991). Reflex bronchoconstriction occurs in several species including humans (Pegelow, 1974, Folkerts and Nijkamp, 1985). Of the three categories of pulmonary sensory receptors whose afferent fibers are carried by the vagus, both RARs (Mills et al., 1969, Vidruk et al., 1977) and C-fibers (Coleridge and Coleridge, 1977, Mohammed et al., 1993) are reported to mediate reflex bronchoconstriction.
Histamine is widely
Acknowledgements
I wish to thank Tracy Duffy for the preparation of the figures and Dr Thomas Pisarri for the critical review of the manuscript.
References (26)
- et al.
Neuropeptides in the respiratory tract
Am. Rev. Respir. Dis.
(1991) - et al.
Characterization of intrapulmonary, rapidly-adapting receptors of guinea pigs
Respir. Physiol.
(1982) - et al.
Identification of vagal sensory receptors in the rat lung: Are there subtypes of slowly adapting receptors?
J. Physiol. (London)
(1993) - et al.
Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs
Respir. Physiol.
(1977) - Flecknell, P.A., 1987. Laboratory Animal Anaesthesia. Academic Press, San Diego,...
- et al.
Haemophilus influenzae induces a potentiated increase in guinea pig pulmonary resistance to histamine
Eur. J. Pharmacol.
(1985) - et al.
An in vitro study of the properties of single vagal afferent innervating guinea pig airways
J. Physiol. (London)
(1993) - et al.
Effects of capsazepine against capsaicin- and proton-evoked excitation of single airway C-fibers and vagus nerve of the guinea-pig
Neuroscience
(1995) - et al.
Bradykinin-induced bronchoconstriction in man: mode of action
Am. Rev. Respir. Dis.
(1987) - et al.
Effects of bradykinin on respiratory rate in anaesthetized rabbits; role of rapidly adapting receptors
J. Physiol. (London)
(1993)
Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons
Pharmacol. Rev.
Afferent neural pathways in cough and reflex bronchoconstriction
J. Appl. Physiol.
Bradykinin stimulates afferent vagal C-fibers in intrapulmonary airways of dogs
J. Appl. Physiol.
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