(S)-Albuterol Increases Intracellular Free Calcium by Muscarinic Receptor Activation and a Phospholipase C-Dependent Mechanism in Airway Smooth Muscle

1998 ◽  
Vol 53 (3) ◽  
pp. 347-354 ◽  
Author(s):  
Sankar Mitra ◽  
Mehmet Ugur ◽  
Ozlem Ugur ◽  
H. Maurice Goodman ◽  
John R. McCullough ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Phospholipase C ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Receptor Activation ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Dependent Mechanism

G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation

2004 ◽  
Vol 286 (2) ◽  
pp. L312-L319 ◽  
Author(s):  
J. K. L. Walker ◽  
R. R. Gainetdinov ◽  
D. S. Feldman ◽  
P. K. McFawn ◽  
M. G. Caron ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
G Protein ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
Muscle Relaxation ◽  
Receptor Activation ◽  
Smooth Muscle Relaxation ◽  
Airway Responses ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) transduce extracellular signals into intracellular events. The waning responsiveness of GPCRs in the face of persistent agonist stimulation, or desensitization, is a necessary event that ensures physiological homeostasis. GPCR kinases (GRKs) are important regulators of GPCR desensitization. GRK5, one member of the GRK family, desensitizes central M2 muscarinic receptors in mice. We questioned whether GRK5 might also be an important regulator of peripheral muscarinic receptor responsiveness in the cardiopulmonary system. Specifically, we wanted to determine the role of GRK5 in regulating muscarinic receptor-mediated control of airway smooth muscle tone or regulation of cholinergic-induced bradycardia. Tracheal pressure, heart rate, and tracheal smooth muscle tension were measured in mice having a targeted deletion of the GRK5 gene ( GRK5- /-) and littermate wild-type (WT) control mice. Both in vivo and in vitro results showed that the airway contractile response to a muscarinic receptor agonist was not different between GRK5- /- and WT mice. However, the relaxation component of bilateral vagal stimulation and the airway smooth muscle relaxation resulting from β2-adrenergic receptor activation were diminished in GRK5- /- mice. These data suggest that M2 muscarinic receptor-mediated opposition of airway smooth muscle relaxation is regulated by GRK5 and is, therefore, excessive in GRK5- /- mice. In addition, this study shows that GRK5 regulates pulmonary responses in a tissue- and receptor-specific manner but does not regulate peripheral cardiac muscarinic receptors. GRK5 regulation of airway responses may have implications in obstructive airway diseases such as asthma or chronic obstructive pulmonary disease.

Muscarinic receptors in airways: recent developments

1990 ◽  
Vol 68 (5) ◽  
pp. 1777-1785 ◽  
Author(s):  
P. J. Barnes
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
Ganglion Cells ◽  
Receptor Activation ◽  
Airway Control ◽  
Submucosal Glands ◽  
Recent Developments ◽  
And Function

Recently there have been important advances in our understanding of muscarinic receptors in airways that have important implications for understanding airway control and for future therapy of airway diseases. The transduction mechanisms involved in muscarinic receptor activation are now better understood. Receptor-linked phosphoinositide hydrolysis leads to release of calcium ions from intracellular stores, resulting in contraction of airway smooth muscle. At least five subtypes of muscarinic receptor have now been cloned, although only three subtypes can be distinguished pharmacologically. M1 receptors are facilitatory to neurotransmission in airway parasympathetic ganglion cells and have also been identified in airway submucosal glands and on the alveolar walls of human lung. M2 receptors are located on postganglionic nerves and function as powerful feedback inhibitory receptors (autoreceptors) that are likely to be involved in modulation of reflex bronchoconstriction. These receptors may be dysfunctional in asthmatic airways. M3 receptors are present on airway smooth muscle and submucosal glands and mediate the classical muscarinic effects in airways. Molecular biology techniques should now allow further study of the factors that regulate transcription and expression of muscarinic receptors in airways.

scholarly journals Indirect muscarinic receptor activation by pentamidine on airway smooth muscle

1996 ◽  
Vol 119 (6) ◽  
pp. 1131-1136 ◽  
Author(s):  
Keltoum Biyah ◽  
Mathieu Molimard ◽  
Emmanuel Naline ◽  
Bernard Bazelly ◽  
Charles Advenier
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Receptor Activation

Silver nanoparticles Induce Anti-Proliferative Effects on Airway Smooth Muscle Cells. Role of Nitric Oxide and Muscarinic Receptor Signaling Pathway

2013 ◽  
Vol 65 ◽  
pp. S104
Author(s):  
Manuel Alejandro Ramirez-Lee ◽  
Hector Rosas-Hernandez ◽  
Samuel Salazar-Garcia ◽  
Jose Manuel Gutiérrez-Hernández ◽  
Ricardo Espinosa- Tanguma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Silver Nanoparticles ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Receptor Signaling Pathway

Characterization of the airway smooth muscle muscarinic receptor in vivo

1991 ◽  
Vol 197 (1-2) ◽  
pp. 109-112 ◽  
Author(s):  
Ralph E. Howell ◽  
Keith Laemont ◽  
Raymond Gaudette ◽  
Maureen Raynor ◽  
Abby Warner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle

ATP stimulates Ca2+oscillations and contraction in airway smooth muscle cells of mouse lung slices

2002 ◽  
Vol 283 (6) ◽  
pp. L1271-L1279 ◽  
Author(s):  
Albrecht Bergner ◽  
Michael J. Sanderson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Phospholipase C ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Mouse Lung ◽  
Airway Smooth Muscle Cells ◽  
Airway Caliber ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

In airway smooth muscle cells (SMCs) from mouse lung slices, ≥10 μM ATP induced Ca2+oscillations that were accompanied by airway contraction. After ∼1 min, the Ca2+oscillations subsided and the airway relaxed. By contrast, ≥0.5 μM adenosine 5′- O-(3-thiotriphosphate) (nonhydrolyzable) induced Ca2+oscillations in the SMCs and an associated airway contraction that persisted for >2 min. Adenosine 5′- O-(3-thiotriphosphate)-induced Ca2+oscillations occurred in the absence of external Ca2+but were abolished by the phospholipase C inhibitor U-73122 and the inositol 1,4,5-trisphosphate receptor inhibitor xestospongin. Adenosine, AMP, and α,β-methylene ATP had no effect on airway caliber, and the magnitude of the contractile response induced by a variety of nucleotides could be ranked in the following order: ATP = UTP > ADP. These results suggest that the SMC response to ATP is impaired by ATP hydrolysis and mediated via P2Y2or P2Y4receptors, activating phospholipase C to release Ca2+via the inositol 1,4,5-trisphosphate receptor. We conclude that ATP can serve as a spasmogen of airway SMCs and that Ca2+oscillations in SMCs are required to sustain airway contraction.

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