Autoradiographic visualization of muscarinic receptors in pulmonary nerves and ganglia

Koppen, Chris J. van; Blankesteijn, W. Matthijs; Klaassen, AndréB.M.; Miranda, J. F. Rodrigues de; Beld, A.J.; Ginneken, C. A. M. Van

doi:10.1016/0304-3940(87)90092-9

Cited by 28 publications

(17 citation statements)

References 5 publications

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“…In the human lung, the M 1 subtype seems to prevail (van Koppen et al, 1988), but the presence of M 2 and M 3 receptors could not be excluded (Mak and Barnes, 1990), whereas in other studies only M 1 but not M 2 and M 3 mRNA were detected (Mak et al, 1992). The expression of M 4 receptor subtype has only been identified in the rabbit lung (Lazareno et al, 1990) as yet (Mak et al, 1992).…”

Section: Introductionmentioning

confidence: 82%

Segment-dependent Expression of Muscarinic Acetylcholine Receptors and G-protein Coupling in the Equine Respiratory Tract

Abraham

Kottke

Ammer³

et al. 2006

Vet Res Commun

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Muscarinic receptors are considered to be of comparable clinical importance in chronic obstructive pulmonary disease (COPD) in equines and in humans. At present, data are scarce on the expression and distribution of probable subtypes of these receptors and their signalling pathways in airway segments, including lung parenchyma and bronchial and tracheal epithelium with the underlying smooth muscle in horses. Specific [N-methyl-3H]scopolamine chloride ([3H]NMS) binding to all three tissues was saturable and of high affinity, with KD values ranging between 1.6+/-0.7 and 1.9+/-0.3 nmol/L. [3H]NMS binding identified a higher density of total muscarinic receptors (fmol/mg protein) in the trachea (720+/-59 nmol/L) than in bronchi (438+/-48 nmol/L) or lung (22 +/- 3 nmol/L). Competitive binding studies using [3H]NMS and the unlabelled subtype-selective antagonists pirenzepine and telenzepine (M1), methoctramine and himbacine (M2), 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (M3), tropicamide (M4) and mamba toxin (MT-3) (M4) indicated the presence of at least three muscarinic receptor subtypes in peripheral lung tissue (50:40:24-28%: M2>M3>M1), whereas in bronchus and trachea M2 subtypes (87-90%) predominated over M3 (14-22%), and M1 subtypes were lacking. No differences were found between tissues in high-affinity binding sites for carbachol in the absence (31-36%) or presence of guanosine 5'-triphosphate (GTP) (approximately 100%). Western blotting for G-protein alpha-subunits showed a much more robust expression of G(alphai1/2) in the trachea (with highest receptor density) than in the lung or bronchi, whereas G(alphas)-protein was dominantly expressed in bronchus. Concomitantly, carbachol inhibited isoproterenol- and GTP-stimulated adenylyl cyclase activity with increasing muscarinic receptor expression (trachea > bronchi > lung). We conclude that the expression and signalling pathways of muscarinic receptors in the equine respiratory tract are segment-dependent. These receptors might contribute to the pathogenesis of COPD in the horse and could provide potential drug targets for the therapeutic use of anticholinergics in this species.

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Section: Introductionmentioning

confidence: 82%

Segment-dependent Expression of Muscarinic Acetylcholine Receptors and G-protein Coupling in the Equine Respiratory Tract

Abraham

Kottke

Ammer³

et al. 2006

Vet Res Commun

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“…The earliest studies of muscarinic receptor distribution in lung tissues employed autoradiographic labeling of muscarinic receptor density in lung sections (van Koppen et al 1987, 1988). These studies demonstrated that muscarinic receptor density is actually highest in parasympathetic ganglia, followed by mucous glands, smooth muscle, and nerve fibers (van Koppen et al 1988).…”

Section: Muscarinic Receptors In the Lungsmentioning

confidence: 99%

“…These studies demonstrated that muscarinic receptor density is actually highest in parasympathetic ganglia, followed by mucous glands, smooth muscle, and nerve fibers (van Koppen et al 1988). Subtype-specific distribution and function has subsequently been determined using pharmacological analysis, in situ hybridization, RT-PCR, and knockout mice.…”

Section: Muscarinic Receptors In the Lungsmentioning

confidence: 99%

“…Both pre- and postganglionic parasympathetic nerves innervating the lungs express muscarinic receptors that are densest at the ganglia (van Koppen et al 1987, 1988). Muscarinic receptors on parasympathetic nerves modulate synaptic neurotransmission between the pre- and postganglionic nerves, and also limit release of acetylcholine by postganglionic nerves at target tissues (smooth muscle, glands).…”

Section: Muscarinic Receptors In the Lungsmentioning

confidence: 99%

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Muscarinic Receptor Antagonists: Effects on Pulmonary Function

Buels

Fryer

2011

Handbook of Experimental Pharmacology

110

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In healthy lungs, muscarinic receptors control smooth muscle tone, mucus secretion, vasodilation, and inflammation. In chronic obstructive pulmonary disease (COPD) and asthma, cholinergic mechanisms contribute to increased bronchoconstriction and mucus secretion that limit airflow. This chapter reviews neuronal and nonneuronal sources of acetylcholine in the lung and the expression and role of M1, M2, and M3 muscarinic receptor subtypes in lung physiology. It also discusses the evidence for and against the role of parasympathetic nerves in asthma, and the current use and therapeutic potential of muscarinic receptor antagonists in COPD and asthma.

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“…These results suggest that M 1 receptors located at the ganglionic level can enhance the vagal reflex caused by HCl intra-oesophageal instillation. Stimulation of muscarinic M 1 receptors has been demonstrated both in animal and human bronchi to cause depolarization in autonomic ganglion cells and to facilitate neurotransmission by concomitant activation of nicotinic receptors (Racké and Matthiesen, 2004;van Koppen et al, 1987van Koppen et al, , 1988. Studies in various species have demonstrated that this increase in nerve transmission through airway parasympathetic ganglia participates in reflex bronchoconstriction (Racké and Matthiesen, 2004;Belmonte, 2005;Coulson and Fryer, 2003).…”

Section: Discussionmentioning

confidence: 96%

Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux

et al. 2008

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Autoradiographic visualization of muscarinic receptors in pulmonary nerves and ganglia

Cited by 28 publications

References 5 publications

Segment-dependent Expression of Muscarinic Acetylcholine Receptors and G-protein Coupling in the Equine Respiratory Tract

Segment-dependent Expression of Muscarinic Acetylcholine Receptors and G-protein Coupling in the Equine Respiratory Tract

Muscarinic Receptor Antagonists: Effects on Pulmonary Function

Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux

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