Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Fryer, A.D.; Maclagan, Jennifer

doi:10.1111/j.1476-5381.1984.tb16539.x

Cited by 300 publications

(221 citation statements)

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“…One reason for the abnormality of the neural control of the airway smooth muscle is the loss of M2 receptor function (M2R). The M2Rs act by limiting the release of acetylcholine (Ach) onto the smooth muscle M3R (39). Thus, loss of M2R leads to uncontrolled smooth muscle contraction and subsequent bronchoconstriction as seen in asthma (40).…”

Section: Tissue Localization and Activation Status Of The Eosinophil mentioning

confidence: 99%

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Adamko

Odemuyiwa

Vethanayagam

et al. 2004

Allergy

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We have entered a new phase in the evolution of our understanding of the role of the eosinophil with a greater appreciation of novel potential functions that may be ascribed to this enigmatic cell type. This review not only provides an update to our current understanding of the various immunobiological roles for the eosinophil, but also attracts attention to some novel observations predicting functions beyond its putative effector role. These observations include the intriguing possibility that the eosinophil may posses the capacity to regulate the immune and inflammatory responses in diseases such as asthma.

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Section: Tissue Localization and Activation Status Of The Eosinophil mentioning

confidence: 99%

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Adamko

Odemuyiwa

Vethanayagam

et al. 2004

Allergy

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“…Contractions were induced by electrical field stimulation (EFS) or by increasing concentrations of methacholine (MCh) as previously described (30). Neuronal M 2 muscarinic receptor function was tested in human tracheal smooth muscle by measuring the ability of gallamine, a selective antagonist, to potentiate EFSinduced contractions (19). Additional details are provided in the online supplement.…”

Section: Bronchoalveolar Lavage and Morphologic Study Of Lungmentioning

confidence: 99%

“…In the lungs, M 2 muscarinic receptors limit acetylcholine (ACh) release from parasympathetic nerves (16)(17)(18), thereby limiting vagally induced bronchoconstriction (19,20). Dysfunctional M 2 muscarinic receptors on airway parasympathetic nerves result in airway hyperresponsiveness in humans with asthma (21)(22)(23) and in animal models of asthma (24)(25)(26).…”

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confidence: 99%

Hyperinsulinemia Potentiates Airway Responsiveness to Parasympathetic Nerve Stimulation in Obese Rats

Nie

Jacoby

Fryer

2014

Am J Respir Cell Mol Biol

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Obesity is a substantial risk factor for developing asthma, but the molecular mechanisms underlying this relationship are unclear. We tested the role of insulin in airway responsiveness to nerve stimulation using rats genetically prone or resistant to diet-induced obesity. Airway response to vagus nerve stimulation and airway M 2 and M 3 muscarinic receptor function were measured in obeseprone and -resistant rats with high or low circulating insulin. The effects of insulin on nerve-mediated human airway smooth muscle contraction and human M 2 muscarinic receptor function were tested in vitro. Our data show that increased vagally mediated bronchoconstriction in obesity is associated with hyperinsulinemia and loss of inhibitory M 2 muscarinic receptor function on parasympathetic nerves. Obesity did not induce airway inflammation or increase airway wall thickness. Smooth muscle contraction to acetylcholine was not increased, indicating that hyperresponsiveness is mediated at the level of airway nerves. Reducing serum insulin with streptozotocin protected neuronal M 2 receptor function and prevented airway hyperresponsiveness to vagus nerve stimulation in obese rats. Replacing insulin restored dysfunction of neuronal M 2 receptors and airway hyperresponsiveness to vagus nerve stimulation in streptozotocintreated obese rats. Treatment with insulin caused loss of M 2 receptor function, resulting in airway hyperresponsiveness to vagus nerve stimulation in obese-resistant rats, and inhibited human neuronal M 2 receptor function in vitro. This study shows that it is not obesity per se but hyperinsulinemia accompanying obesity that potentiates vagally induced bronchoconstriction by inhibiting neuronal M 2 muscarinic receptors and increasing acetylcholine release from airway parasympathetic nerves.Keywords: hyperinsulinemia; obesity; asthma; airway responsiveness; neural M 2 muscarinic receptor Clinical RelevanceObesity-induced asthma does not respond well to traditional anti-inflammatory therapies, suggesting that it is a unique asthma phenotype. Here we show that hyperinsulinemia causes airway hyperresponsiveness to vagus nerve stimulation in obese rats. In human trachea and in rats, we demonstrate that insulin inhibits M 2 muscarinic receptors on airway parasympathetic nerves, resulting in increased acetylcholine release and increased airway contraction. Because hyperinsulinemia is greater and more prevalent in obese individuals, these data may explain why obese individuals are prone to asthma exacerbations and suggest that anticholinergic drugs may be effective in this specific phenotype of asthma.In the United States, 31% of adults and 15% of children are obese. In obese and overweight individuals, the prevalence of asthma (1-3) and the rate of new-onset asthma have increased (4-6). Obese patients with asthma also have increased severity of illness and reduced effectiveness of steroids compared with nonobese patients with asthma (1, 6, 7). The mechanisms by which obesity predisposes to asthma are unclear, limi...

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“…Loss of function of inhibitory muscarinic autoreceptors is characterized by airway hyperresponsiveness to electrical stimulation of the vagus nerve. Furthermore, airway hyperresponsiveness to histamine in antigen challenged guinea pigs is due to increased vagally mediated reflex bronchoconstriction as a result of M2 receptor dysfunction (1)(2)(3)(4). It has been demonstrated that both in humans and in experimental animals the airway hyperresponsiveness, observed during viral infections, is the result of increased reflex bronchoconstriction due to inhibition of M2 muscarinic receptors.…”

Section: Introductionmentioning

confidence: 99%

Effects of neuraminidase on equine isolated bronchi

Matera¹,

Calzetta²,

Sanduzzi³

et al. 2008

Pulmonary Pharmacology & Therapeutics

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A c c e p t e d m a n u s c r i p t AbstractIt has been demonstrated in mammals that the airway hyperresponsiveness which accompanies viral infections is the result of increased reflex bronchoconstriction due to inhibition of muscarinic prejunctional receptors, which belong to M2 subtypes. Multiple mechanisms account for virus-induced M2 receptor dysfunction. Viral neuraminidase may deglycosylate the M2 receptor, decreasing acetylcholine affinity. Equine influenza remains a common viral respiratory disease of horses worldwide, which results in loss to the equine industry, by decreasing performance, convalescence time and loss of peak performance due to chronic sequelae, such as airway hyperresponsiveness. The purpose of this study was to evaluate the effect of neuraminidase on equine isolated bronchi, assessed in equine bronchial smooth muscle rings, derived from five healthy equine male lungs. A pretreatment with vehicle did not modify contraction induced by EFS at each frequency tested. A pretreatment with pilocarpine (1 to 100 μM) significantly reduced, while methoctramine (1 to 100 μM) significantly increased contraction induced by EFS. Finally neuraminidase (0.5 Ul) significantly increased contraction induced by EFS. These results suggest that airway hyperresponsiveness that follows a viral influenza infection might be related to a dysfunction of muscarinic prejunctional receptors.

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Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Cited by 300 publications

References 10 publications

The rise of the phoenix: the expanding role of the eosinophil in health and disease

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Hyperinsulinemia Potentiates Airway Responsiveness to Parasympathetic Nerve Stimulation in Obese Rats

Effects of neuraminidase on equine isolated bronchi

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