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Journal ArticleDOI

Localization of muscarinic receptor subtype mRNAs in human lung.

TLDR
With the exception of the airway epithelium, there was a good correlation between the distribution of mRNAs by in situ hybridization and the distributionof receptor subtypes by autoradiographic mapping.
Abstract
m2 mRNA in airway smooth muscle; m3 mRNA in airway epithelium, airway smooth muscle, and submucosal glands. No detection of m4 and m5 mRNAs was observed in any cellular structures. The presence of various muscarinic receptor subtype mRNAs was confirmed by Northern blot analysis. Only human lung mRNA hybridized to the m1 probe giving a single 3.2 kb transcript. mRNA from the human cultured airway smooth muscle cells gave m2 and m3 hybridization bands of about 6.0 kb and 4.5 kb, respectively, while mRNA from the cultured airway epithelial cells gave only m3 hybridization band of 4.5 kb. With the exception of the airway epithelium, there was a good correlation between the distribution of mRNAs by in situ hybridization and the distribution of receptor subtypes by autoradiographic mapping. These results may have an important clinical implication, and also give rise to further investigation of gene regulation of pulmonary muscarinic receptor subtypes in health and disease.

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Journal ArticleDOI

Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: Expression and function in humans

TL;DR: The most important tasks for the future will be to clarify the multiple biological roles of non-neuronal acetylcholine in detail and to identify pathological conditions in which this system is up- or down-regulated, which could provide the basis for the development of new therapeutic strategies to target the non-NEuronal cholinergic system.
Journal ArticleDOI

Signaling and regulation of G protein-coupled receptors in airway smooth muscle

TL;DR: This review provides a comprehensive overview of the GPCRs that have been identified in ASM cells, and discusses the extent to which signaling via these GPCR has been characterized and linked to distinct ASM functions.
Journal ArticleDOI

Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function.

TL;DR: The availability of novel and selectivemuscarinic agonists and antagonists, as well as in vivo gene disruption techniques, has clarified the roles of muscarinic receptors in mediating both functions of acetylcholine.
Journal ArticleDOI

Muscarinic receptor subtypes in airways

TL;DR: Muscarinic receptor subtypes in the airways appear to subserve different physiological functions and anticholinergic drugs which selectively block M3 and M1-receptors may have an advantage over currently used non-selective antagonists in the treatment of airway obstruction.
Journal ArticleDOI

Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease.

TL;DR: The future for inhaled anticholinergic compounds for the treatment of chronic obstructive pulmonary disease appears to rest in their combination with other agents, such as beta2 agonists and phosphodiesterase-4 inhibitors.
References
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Journal ArticleDOI

Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction

TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
Journal ArticleDOI

Identification of a family of muscarinic acetylcholine receptor genes

TL;DR: Analysis of human and rat genomic clones indicates that there are at least four functional muscarinic receptor genes and that these genes lack introns in the coding sequence.
Journal ArticleDOI

Muscarinic Receptor Subtypes

TL;DR: The aim of this review is to discuss the structure, function, and binding properties of the different muscarinic receptor species, attempting where possible to coordinate the diverse experimental data into a uniform picture.
Journal ArticleDOI

Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.

TL;DR: Differences among subtypes in the affinities and proportions of such sites suggest the capacity of mAChR subtypes to interact differentially with the cellular effector‐coupling apparatus.
Journal Article

Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.

TL;DR: The diverse binding profiles of individual cloned receptors and the widespread distribution of m1-m4 mRNAs indicate that radioligand binding studies performed on primary tissues may actually be assessing the composite properties of a heterogeneous mixture of muscarinic receptor subtypes.
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