scholarly journals Functional Characterization of Muscarinic Receptors in Human Schwann Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6666
Author(s):  
Roberta Piovesana ◽  
Alessandro Faroni ◽  
Ada Maria Tata ◽  
Adam J. Reid

Functional characterization of muscarinic cholinergic receptors in myelinating glial cells has been well described both in central and peripheral nervous system. Rat Schwann cells (SCs) express different muscarinic receptor subtypes with the prevalence of the M2 subtype. The selective stimulation of this receptor subtype inhibits SC proliferation, improving their differentiation towards myelinating phenotype. In this work, we describe for the first time that human SCs are cholinoceptive as they express several muscarinic receptor subtypes and, as for rat SCs, M2 receptor is one of the most abundant. Human SCs, isolated from adult nerves, were cultured in vitro and stimulated with M2 muscarinic agonist arecaidine propargyl ester (APE). Similarly to that observed in rat, M2 receptor activation causes a decreased cell proliferation and promotes SC differentiation as suggested by increased Egr2 expression with an improved spindle-like shape cell morphology. Conversely, the non-selective stimulation of muscarinic receptors appears to promote cell proliferation with a reduction of SC average cell diameter. The data obtained demonstrate that human SCs are cholinoceptive and that human cultured SCs may represent an interesting tool to understand their physiology and increase the knowledge on how the cholinergic stimulation may contribute to address human SC development in normal and pathological conditions.

1988 ◽  
Vol 65 (2) ◽  
pp. 594-600 ◽  
Author(s):  
T. B. Casale ◽  
P. Ecklund

To better define the role of muscarinic receptors in lung responses and airway diseases, we characterized the binding of the M1-specific antagonist, [3H]pirenzepine (PZ), and the nonspecific (M1- and M2-) antagonist, [3H]quinuclidinyl benzilate (QNB), to human peripheral lung tissue. Data obtained from 15 different lung specimens showed that the radioligands bound to single high-affinity sites with dissociation constant (Kd) values ranging from 1 to 9 nM for [3H]PZ and 0.03 to 0.46 nM for [3H]QNB. Comparison of total binding capacity values by equilibrium experiments with [3H]PZ, unlabeled PZ, and [3H]QNB indicates that approximately one-half of the total muscarinic binding sites in human peripheral lung binds PZ with high affinity (putative M1-subtypes). Kd values for muscarinic agents determined by competition experiments with [3H]PZ were consistent with the expected rank order of potency for interactions with muscarinic receptors. Characterization of the role of these muscarinic receptor subtypes in human lung responses may lead to the development of more selective therapeutic agents for the treatment of chronic obstructive airway diseases.


2001 ◽  
Vol 77 (5) ◽  
pp. 1396-1406 ◽  
Author(s):  
Fadi Ragheb ◽  
Eduardo Molina-Holgado ◽  
Qiao-Ling Cui ◽  
Amani Khorchid ◽  
Hsueh-Ning Liu ◽  
...  

Hypertension ◽  
1995 ◽  
Vol 26 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Tobias A. Bruning ◽  
Peter C. Chang ◽  
Maarten G.C. Hendriks ◽  
Pieter Vermeij ◽  
Martin Pfaffendorf ◽  
...  

1997 ◽  
Vol 273 (3) ◽  
pp. R896-R904 ◽  
Author(s):  
H. A. Baghdoyan

Microinjecting cholinomimetics into the pontine reticular formation produces a state that resembles natural rapid eye movement (REM) sleep. Evocation of this REM sleeplike states is anatomically site dependent within the pons and is mediated by muscarinic receptors. The cellular and molecular mechanisms underlying cholinergic REM sleep generation and muscarinic receptor subtype involvement remain to be specified. This study tested the hypothesis that muscarinic receptor subtypes are differentially distributed within the oral and caudal divisions of rat pontine reticular nucleus. In vitro receptor autoradiography was used to localize and quantify M1, M2, and M3 binding sites in the pontine reticular formation and in pontine brain stem regions known to regulate REM sleep. M1-M3 binding sites were present in some REM sleep-related nuclei, such as dorsal raphe and locus ceruleus. The pontine reticular formation was found to have a homogeneous distribution of M2 binding sites across its rostral to caudal extent, indicating that anatomic specificity of cholinergic REM sleep induction cannot be accounted for by a differential density of muscarinic receptors.


2001 ◽  
Vol 281 (6) ◽  
pp. L1420-L1424 ◽  
Author(s):  
Jiunu Lai ◽  
Xuesi M. Shao ◽  
Richard W. Pan ◽  
Edward Dy ◽  
Cindy H. Huang ◽  
...  

Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspiratory neurons in the pre-Bötzinger complex (pre-BötC), the hypothesized site for respiratory rhythm generation. Because pharmacological tools for identifying the subtypes of the muscarinic receptors that underlie these effects are limited, we probed for mRNA for these receptors in the pre-BötC. We used RT-PCR to determine the expression of muscarinic receptor subtypes in tissue punches of the pre-BötC taken from rat medullary slices. Cholinergic receptor subtype M2 and M3 mRNAs were observed in the first round of PCR amplification. All five subtypes, M1–M5, were observed in the second round of amplification. Our results suggest that the majority of muscarinic receptor subtypes in the pre-BötC are M2 and M3, with minor expression of M1, M4, and M5.


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