Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.

Okayama, Michiko; T, Shen; Midorikawa, Jun; Lin, Jiang-Tao; Inoue, Hiroshi; Takishima, Tamotsu; Shirato, Kunio

doi:10.1164/ajrccm.149.1.8111602

Cited by 19 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be of some significance, as loss of AChE activity would be expected to lead to increased neurotransmission via ACh and augment the effect of the other changes seen in this system (i.e., increased cholinergic activity). There have been prior studies in a number of animal models of loss of function of acetylcholinesterase (27,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). The observation of decreased acetylcholinesterase activity in the context of a modest increase in acetylcholinesterase protein expression may seem contradictory.…”

Section: Discussionmentioning

confidence: 99%

Eosinophil-Mediated Cholinergic Nerve Remodeling

Durcan

Costello²,

McLean³

et al. 2006

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling. We hypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M 2 muscarinic receptor, with this induction being mediated via an adhesion-dependent release of eosinophil proteins, including major basic protein and nerve growth factor. Studies on the promoter sequence of the M 2 receptor indicated that this induction was initiated at a transcription start site 145 kb upstream of the gene-coding region. This promoter site contains binding sites for a variety of transcription factors including SP1, AP1, and AP2. Eosinophils also induced the expression of several cholinergic genes involved in the synthesis, storage, and metabolism of acetylcholine, including the enzymes choline acetyltransferase, vesicular acetylcholine transferase, and acetylcholinesterase. The observed eosinophil-induced changes in enzyme content were associated with a reduction in intracellular neural acetylcholine but an increase in choline content, suggesting increased acetylcholine turnover and a reduction in acetylcholinesterase activity, in turn suggesting reduced catabolism of acetylcholine. Together these data suggest that eosinophil localization to cholinergic nerves induces neural remodeling, promoting a cholinergic phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

Eosinophil-Mediated Cholinergic Nerve Remodeling

Durcan

Costello²,

McLean³

et al. 2006

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…This may equally apply to man, since dysfunction of these receptors has been observed in stable mild human asthmatics (Ayala & Ahmed, 1989;Minette et al, 1989). It remains to be established, however, whether or not M2 receptor dysfunction in such patients is reversible with time, since a recent study suggests that these receptors are at least in part functioning in stable asthmatic airways (Okayama et al, 1994). This work was supported by the Netherlands Asthma Foundation (NAF-grant 88.39).…”

Section: Muscarinic Receptor Dysfunction and In Vivo Airway Responsesmentioning

confidence: 96%

Dysfunction of muscarinic M₂ receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea‐pigs

Berge

Santing

Hamstra

et al. 1995

British J Pharmacology

View full text Add to dashboard Cite

1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, cardiac M2 receptor function in vitro and bronchial responsiveness to histamine in vivo were evaluated. 2. Sensitivity to inhaled histamine was increased 3.1 fold and 1.6 fold after the early and late allergic reactions (i.e. at 5 h and 23 h after a single ovalbumin challenge), respectively. At 23 h after the last of four allergen challenges, executed on four consecutive days, bronchial hyperresponsiveness to histamine was diminished to 1.3 fold. 3. After the early response, there was no change in cardiac muscarinic M2 receptor function, since in left atria pD2 (-log EC50) and Emax values of pilocarpine and pKB values of AQ-RA 741, a selective M2 receptor antagonist, were not significantly different from controls (unchallenged sensitized animals), and this also applied to methacholine pD2 values for muscarinic M3 receptors in tracheal smooth muscle. 4. Prejunctional inhibitory muscarinic M2 autoreceptors in airway smooth muscle were markedly dysfunctional after the early allergic response, since potentiation of electrically evoked twitch contractions of tracheal preparations by low concentrations of the M2-selective muscarinic receptor antagonists, gallamine, methoctramine, AQ-RA 741 and AF-DX 116, which is the result of M2 receptor blockade, was clearly and significantly diminished compared to controls. However, after the late response, both in single and repeatedly challenged animals, twitch potentiation was not significantly different from and similar to controls, indicating restoration of M2 receptor function during the late allergic reaction.5. It is concluded that dysfunction of muscarinic M2 autoreceptors in the airways of sensitized and challenged guinea-pigs is already present after the early allergic reaction, and that it has recovered after the late response. Since histamine-induced bronchoconstriction involves vagal pathways, the present results suggest that bronchial hyperresponsiveness to histamine is partly due to M2 auto receptor dysfunction, leading to increased release of acetylcholine.

show abstract

“…In allergic guinea pigs, the magnitude of the early asthmatic reaction has been reported to correlate significantly with the extent of M 2 autoreceptor dysfunction [142]. M 2 autoreceptors have also been found to be dysfunctional in some but not all asthmatics [143][144][145]. In addition, asthmatics with active viral infections show greater bronchodilatory responses to inhaled anticholinergics, suggesting increased vagal tone [146].…”

Section: Cholinergic Mechanismsmentioning

confidence: 99%

Airway hyperresponsiveness in asthma: lessons fromin vitromodel systems and animal models: Fig. 1—

Gosens¹,

Zaagsma²

2008

Eur Respir J

107

View full text Add to dashboard Cite

Airway hyperresponsiveness (AHR) is a hallmark clinical symptom of asthma. At least two components of AHR have been identified: 1) baseline AHR, which is persistent and presumably caused by airway remodelling due to chronic recurrent airway inflammation; and 2) acute and variable AHR, which is associated with an episodic increase in airway inflammation due to environmental factors such as allergen exposure.Despite intensive research, the mechanisms underlying acute and chronic AHR are poorly understood. Owing to the complex variety of interactive processes that may be involved, in vitro model systems and animal models are indispensable to the unravelling of these mechanisms at the cellular and molecular level.The present paper focuses on a number of translational studies addressing the emerging central role of the airway smooth muscle cell, as a multicompetent cell involved in acute airway constriction as well as structural changes in the airways, in the pathophysiology of airway hyperresponsiveness.

show abstract

Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.

Cited by 19 publications

References 20 publications

Eosinophil-Mediated Cholinergic Nerve Remodeling

Eosinophil-Mediated Cholinergic Nerve Remodeling

Dysfunction of muscarinic M₂ receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea‐pigs

Airway hyperresponsiveness in asthma: lessons fromin vitromodel systems and animal models: Fig. 1—

Contact Info

Product

Resources

About

Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.

Cited by 19 publications

References 20 publications

Eosinophil-Mediated Cholinergic Nerve Remodeling

Eosinophil-Mediated Cholinergic Nerve Remodeling

Dysfunction of muscarinic M2 receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea‐pigs

Airway hyperresponsiveness in asthma: lessons fromin vitromodel systems and animal models: Fig. 1—

Contact Info

Product

Resources

About

Dysfunction of muscarinic M₂ receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea‐pigs