A possible role of a nonadrenergic inhibitory nervous system in airway hyperreactivity

Aizawa, Hisamichi; Matsuzaki, Yoshio; Ishibashi, Masayoshi; Domae, Mariko; Hirose, Takahito; Shigematsu, Nobuaki; Tanaka, Kenzö

doi:10.1016/0034-5687(82)90017-2

Cited by 22 publications

(19 citation statements)

References 18 publications

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“…Disorder of the autonomic nervous system is involved in airway hyperresponsiveness. Such abnormalities include enhanced cholinergic and eNANC mechanisms [26,30,31], or reduced β-adrenergic [32] and inhibitory NANC mechanisms [33]. PACAP directly relaxed the airway smooth muscle, and in addition, inhibited the release of ACh or SP from nerve termini in this study.…”

Section: Discussionmentioning

confidence: 58%

Pituitary adenylate cyclase activating peptide regulates neurally mediated airway responses

Shigyo¹,

Aizawa²,

Inoue³

et al. 1998

Eur Respir J

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Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like peptide that has been purified from the ovine hypothalami [1]. PACAP has the same potency as VIP in relaxing airway and vascular smooth muscle [2][3][4][5]. Recently, it has been demonstrated that PACAP induced bronchodilatation in animals treated with histamine or allergen [6]. However, the pathophysiological roles of PACAP in mammalian airways have not been fully elucidated. The structural and functional homology between PACAP and VIP makes it likely that PACAP may participate in the modulation of airway responses in a similar manner to VIP.VIP immunoreactivity is localized to the vagus nerve in the smooth muscle of mammalian airways [7][8][9]. It has been reported that VIP inhibits cholinergic neuroeffector transmission by suppressing acetylcholine (ACh) release from vagal nerve termini [10]. PACAP may have the same effects on cholinergic nerves. It has also been reported that VIP suppresses the smooth muscle contraction evoked by substance P (SP) [11]. SP belongs to the tachykinin family and is released from bronchial C-fibres, causing smooth muscle contraction and plasma extravasation [12].Increased plasma extravasation and smooth muscle contraction mediated by the vagus nerve may contribute to the airway hyperresponsiveness and inflammation observed in asthma. However, it is not known whether SP and PACAP interact.For these reasons, in the present study, we examined the roles of PACAP involved in airway smooth muscle response and plasma extravasation induced by cholinergic and excitatory nonadrenergic noncholinergic (eNANC) nerves in guinea-pigs. Methods Immunohistochemical examinationLungs were dissected out from three guinea-pigs after sacrifice. The specimens were immersed for 12 h in an ice-cold fixative solution composed of 2% formaldehyde buffered to pH 7.2 with 0.1 M phosphate buffer and 0.2% picric acid. They were then rinsed in a Tyrode solution containing 10% sucrose for 48 h, frozen on dry ice, and sectioned by a cryostat at a thickness of 10 µm. Then, they were immersed in sucrose-enriched Tyrode solution for 24-48 h, briefly rinsed in 0.1 M phosphate buffer (pH 7.4), and stretched on chrome-alum subbed glass slides as whole mounts. Cryostat sections and whole mounts were processed for immunohistochemical demonstration of PACAP using an avidin-biotin complex method. The PACAP antiserum (Yanaihara Institute Inc., Shizuoka, Japan) was raised in a rabbit against human PACAP 27 or PACAP 38 and used at a dilution of 1:12,000. The sections were exposed to the peptide antiserum for 4 h at room temperature. The antigen-antibody reaction was demonstrated by application of biotin-labelled anti-rabbit immunoglobulin G (IgG) Smooth muscle contraction evoked by electrical field stimulation (EFS) or exogenously applied acetylcholine (ACh) or substance P (SP) was measured before and after PACAP in vitro. The effect of PACAP on airway plasma extravasation was also measured in vivo.In trachea, PACAP (10 -9 -10 -...

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Section: Discussionmentioning

confidence: 58%

Pituitary adenylate cyclase activating peptide regulates neurally mediated airway responses

Shigyo¹,

Aizawa²,

Inoue³

et al. 1998

Eur Respir J

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“…Inhibitory-NANC relaxation has also been demonstrated in vivo in healthy subjects, which can be activated by inhalation of capsaicin [30,31] or sulphur dioxide [32], or by laryngeal stimulation [33]. Inhibition of the i-NANC system by hexamethonium or vagotomy induces airway hyperresponsiveness in cats, suggesting a possible role of i-NANC in the genesis of bronchial asthma [34,35]. In asthmatic subjects, it has been suggested that the i-NANC system may play a crucial role in nocturnal asthma, based upon the observation that i-NANC relaxation was reduced in the early morning [36].…”

Section: Discussionmentioning

confidence: 99%

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

Aizawa

Tanaka²,

Sakai³

et al. 1997

Eur Respir J

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The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N ω -nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat.To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10 -5 M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin.These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation. Eur Respir J 1997; 10: 314- Neurally-mediated relaxation of airway smooth muscle in various animal species, including man, is largely nonadrenergic and noncholinergic (NANC) (see, for example, [1]). Although the neurotransmitter(s) responsible for NANC relaxation in the airways have not been conclusively identified, nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) have emerged as strong candidates [2][3][4][5][6][7].In cat airway, we have shown that NANC relaxation can be classified into two components by thresholds for activation or by sensitivity to N ω -nitro-L-arginine methylester (L-NAME), and that the pattern of L-NAME-sensitive and -insensitive components differs in central and peripheral airways [6,7]. Specifically, electrical field stimulation (EFS) elicited monophasic relaxation in the trachea, confirming previous observations [5,8], but biphasic NANC relaxations, comprising an initial fast component followed by a second slow component in the bronchioles. L-NAME selectively abolished the first component of NANC relaxation without affecting the second in bronchioles, whilst, in the trachea, L-NAME completely suppressed the monophasic NANC relaxation after single or short repetitions (<5) of 1 ms pulse stimuli; however, after more stimuli (>10) of 1 or 4 ms duration, suppression of NANC relaxation was incomplete (to 40-50% of the control value) [7]. VIP antagonists partially suppressed the L-NAME-resistant NANC relaxation....

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“…The NAIS is the principal inhibitory ner vous system in human airways and it has been suggested to play an important role in bron chial hyperreactivity [17,35], A possible in hibitory influence of adenosine on this system could be very interesting and open up new perspectives for the comprehension and the treatment of the asthmatic disorder.…”

Section: Discussionmentioning

confidence: 99%

Adenosine Enhances the Bronchocontractile Response to Histamine in Anaesthetized and Curarized Guinea Pigs through a Mechanism Partly Blocked by Hexamethonium

Breschi¹,

Nieri²,

Lazzeri³

et al. 1994

Pharmacology

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The ability of adenosine to potentiate the airway narrowing induced by histamine in anaesthetized and curarized guinea pigs has been investigated in order to establish whether it could be ascribed to a modulatory activity by the nucleoside at the neuronal level. Bilateral vagotomy, atropine (2 mg/kg i.v.), and pretreatment with capsaicin (52 mg/kg s.c. 6 days before the experiment) did not result in any significant protection against the enhancement provoked by the nucleoside of the bronchocontractile effect of histamine. On the contrary, the latter was significantly reduced by the ganglionic blocking agent, hexamethonium (10 mg/kg i.v.). Moreover, the effect of adenosine on airway responsiveness to histamine was not modified in animals treated with propranolol (1 mg/kg i.v.) or guanethidine (20 mg/kg s.c. over a period of 2 days). In conclusion, current data suggest that the purine is able, in our experimental model, to potentiate the bronchospasm induced by histamine by means of a mechanism mediated, at least partly, by non-adrenergic-non-cholinergic nerves not related to capsaicin-sensitive afferent neurons.

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A possible role of a nonadrenergic inhibitory nervous system in airway hyperreactivity

Cited by 22 publications

References 18 publications

Pituitary adenylate cyclase activating peptide regulates neurally mediated airway responses

Pituitary adenylate cyclase activating peptide regulates neurally mediated airway responses

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

Adenosine Enhances the Bronchocontractile Response to Histamine in Anaesthetized and Curarized Guinea Pigs through a Mechanism Partly Blocked by Hexamethonium

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