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Second M muscarinic receptor binding site contributes to bronchoprotection by tiotropium.
Br J Pharmacol
August 2019
Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.
Background And Purpose: The bronchodilator tiotropium binds not only to its main binding site on the M muscarinic receptor but also to an allosteric site. Here, we have investigated the functional relevance of this allosteric binding and the potential contribution of this behaviour to interactions with long-acting β-adrenoceptor agonists, as combination therapy with anticholinergic agents and β-adrenoceptor agonists improves lung function in chronic obstructive pulmonary disease.
Experimental Approach: ACh, tiotropium, and atropine binding to M receptors were modelled using molecular dynamics simulations.
Role of sphingosine-1-phosphate inβ-adrenoceptor desensitization via Ca(2+) sensitization in airway smooth muscle.
Allergol Int
June 2012
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan.
Background: The correlation between inflammatory cells and airway smooth muscle plays fundamental roles in the pathophysiology of asthma. This study was designed to determine whether pre-exposure of airway smooth muscle to sphingosine-1-phosphate (S1P), which is released from mast cells by allergic reactions, causes a deterioration of β-adrenoceptor function.
Methods: Isometric tension and the ratio of fluorescence intensities at 340 and 380 nm (F(340)/F(380)), an indicator of intracellular Ca2+ levels, were simultaneously measured using fura-2 loaded guinea-pig tracheal tissues.
Role of the endocannabinoid system in ethanol-induced inhibition of salivary secretion.
Alcohol Alcohol
January 2010
Cátedra de Fisiología, Universidad de Buenos Aires, Argentina.
Article Synopsis
- The study aimed to explore the role of the endocannabinoid system in how ethanol affects saliva production in male Wistar rats.
- Different methods were used to measure salivary secretion and arachidonoyl ethanolamide (anandamide) levels after administering ethanol, including blocking cannabinoid receptors.
- Results showed that ethanol increased AEA levels and inhibited saliva secretion, effects that were partially reversed by blocking cannabinoid receptors, suggesting that the endocannabinoid system mediates ethanol's impact on salivation.
Role of Ca(2+) mobilization in desensitization of beta-adrenoceptors by platelet-derived growth factor in airway smooth muscle.
Eur J Pharmacol
September 2008
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Platelet-derived growth factor (PDGF), which is released from eosinophils and fibroblasts, may be implicated in the pathophysiology of bronchial asthma. To examine the involvement of airway inflammation in beta-adrenergic desensitization, the present study was designed to determine whether pre-exposure to PDGF deteriorates beta-adrenoceptor function in airway smooth muscle. We focused on Ca(2+) signaling as an intracellular mechanism involved in this phenomenon.
View Article and Find Full Text PDFInvolvement of reduced sensitivity to Ca in beta-adrenergic action on airway smooth muscle.
Clin Exp Allergy
February 2006
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Background: It is well known that beta-adrenoceptor agonists (beta-agonists) cause relaxation in airway smooth muscle mediated by a reduction in the concentration of intracellular Ca2+ ([Ca2+](i)). However, little is currently known regarding whether reduced sensitization to Ca2+ is involved in the beta-adrenergic relaxation.
Objective: This study was designed to determine the intracellular mechanisms underlying suppression of Ca2+ sensitization in beta-adrenergic relaxation (Ca(2+)-independent relaxation by beta-agonists).
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