From the Guidelines
The airways are primarily equipped with muscarinic receptor subtypes, including M1, M2, and M3, which play significant roles in regulating airway smooth muscle constriction and relaxation. These receptors are crucial in the pathophysiology of respiratory diseases such as asthma and COPD, as evidenced by the study published in the Journal of Allergy and Clinical Immunology in 2016 1. The M1 subtype is localized to parasympathetic ganglia, the M2 subtype provides feedback inhibition on postganglionic cholinergic nerve terminals, and the M3 subtype is responsible for releasing acetylcholine, which constricts airway smooth muscle.
Key aspects of these receptors include:
- The M3 subtype's role in mediating bronchoconstriction when activated by acetylcholine, making anticholinergics like tiotropium effective bronchodilators, as discussed in the context of asthmatic patients and patients with COPD 1.
- The importance of understanding the distribution and function of these muscarinic receptor subtypes in the development of therapeutic strategies for respiratory diseases.
- The involvement of parasympathetic neural activity in both asthmatic patients and patients with COPD, highlighting the potential benefits of targeting these pathways in treatment plans.
In the context of real-life clinical medicine, recognizing the presence and function of muscarinic receptors in the airways is vital for selecting appropriate pharmacological interventions, such as anticholinergic medications, to manage symptoms and improve quality of life for patients with respiratory conditions.
From the FDA Drug Label
Tiotropium is a long-acting, muscarinic antagonist which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation Olodaterol is a long-acting beta2-adrenergic agonist (LABA). The compound exerts its pharmacological effects by binding and activation of beta2-adrenoceptors after topical administration by inhalation Beta-adrenoceptors are divided into three subtypes: beta1-adrenoceptors predominantly expressed on cardiac muscle, beta2-adrenoceptors predominantly expressed on airway smooth muscle, and beta3-adrenoceptors predominantly expressed on adipose tissue.
The airways contain muscarinic receptors (M1 to M5) and beta2-adrenoceptors. These receptors play a crucial role in regulating airway smooth muscle tone. The muscarinic receptors, specifically M3-receptors, are involved in bronchoconstriction, while the beta2-adrenoceptors are involved in bronchodilation 2.
From the Research
Receptors in the Airways
The airways contain various receptors that play crucial roles in regulating respiratory functions. Some of the key receptors found in the airways include:
- Beta-2 adrenergic receptors (β2-ARs) [ 3, 4, 5, 6, 7 ], which are primarily localized on airway smooth muscle cells and are involved in bronchodilation
- Muscarinic receptors, specifically M(3) receptors [ 6 ], which are targeted by anticholinergic bronchodilators
- Glucocorticoid receptors (GR) [ 6 ], which are widely distributed and targeted by corticosteroids
- Cysteinyl-leukotriene 1 receptors [ 6 ], which are mainly expressed in airway smooth muscle and targeted by antileukotrienes
- Chemotactic receptors [ 6 ], which are involved in the recruitment of inflammatory cells into the airways
Distribution and Function of Receptors
The distribution and function of these receptors vary, with some being specific to certain cell types or regions of the airways. For example:
- β2-ARs are expressed on airway smooth muscle cells, mast cells, and postcapillary venules [ 4, 6 ]
- Muscarinic receptors are found on airway smooth muscle cells, particularly in small airways [ 6 ]
- Glucocorticoid receptors are widely distributed, making inhalation a effective delivery method to minimize systemic side effects [ 6 ]