scholarly journals The Mechanism of Choline-Mediated Inhibition of Acetylcholine Release in Mouse Motor Synapses

Acta Naturae ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 110-115 ◽  
Author(s):  
A. E. Gaydukov ◽  
P. O. Bogacheva ◽  
E. O. Tarasova ◽  
O. P. Balezina
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Neurotransmitter Release ◽  
Acetylcholine Receptors ◽  
Acetylcholine Release ◽  
Ryanodine Receptors ◽  
Inhibitory Effect ◽  
Quantal Content ◽  
Kca Channels ◽  
Miniature Endplate Potentials ◽  
Endplate Potentials

The mechanism of action of tonically applied choline, the agonist of 7 nicotinic acetylcholine receptors (nAChRs), to the spontaneous and evoked release of a neurotransmitter in mouse motor synapses in diaphragm neuromuscular preparations using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) was studied. Exogenous choline was shown to exhibit a presynaptic inhibitory effect on the amplitude and quantal content of EPPs for the activity of neuromuscular junction evoked by single and rhythmic stimuli. This effect was inhibited either by antagonists of 7-nAChRs, such as methyllycaconitine and -cobratoxin, or by blocking SK-type calcium-activated potassium (K Ca) channels with apamin or blocking intraterminal ryanodine receptors with ryanodine. A hypothesis was put forward that choline in mouse motoneuron nerve terminals can activate presynaptic 7-nAChRs, followed by the release of the stored calcium through ryanodine receptors and activation of SK-type KCa channels, resulting in sustained decay of the quantal content of the evoked neurotransmitter release.

scholarly journals Resistance to d-Tubocurarine of the Rat Diaphragm as Compared to a Limb Muscle

2009 ◽  
Vol 110 (5) ◽  
pp. 1011-1015 ◽  
Author(s):  
Tu Nguyen-Huu ◽  
Jordi Molgó ◽  
Denis Servent ◽  
Philippe Duvaldestin
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Binding Sites ◽  
Acetylcholine Receptors ◽  
Neuromuscular Blocking ◽  
Quantal Content ◽  
Nicotinic Acetylcholine ◽  
The Mean ◽  
Edl Muscle ◽  
Alpha Bungarotoxin ◽  
Endplate Potentials

Background The diaphragm is resistant to competitive neuromuscular blocking agents, as compared to peripheral muscles. The basis of this difference may be a higher concentration of acetylcholine released or higher number of postsynaptic nicotinic acetylcholine receptors in diaphragmatic neuromuscular junctions. Methods Nerve-evoked twitch-tension was measured in rat hemidiaphragm as was Extensor digitorum longus (EDL) nerve-muscle preparation to determine the effective D-tubocurarine concentration that decreased twitch responses by 50%. The mean quantal content of endplate potentials was determined in single junctions in a low-Ca(2+), high-Mg(2+) Krebs-Ringer medium. Strips of hemidiaphragm and EDL muscle, containing the endplate regions, were used to determine the number of nAChR nicotinic acetylcholine receptor binding sites with the aid of radiolabeled [(125)I]alpha-bungarotoxin. Results The effective D-tubocurarine concentration that decreased twitch responses by 50% (median [interquartile range]) was seven-fold higher in the hemidiaphragm than in the EDL (1.82 microm [1.43-2.20] vs. 0.26 microm [0.23-0.29], P < 0.01). The median of the mean quantal content was higher in the hemidiaphragm than in the EDL (0.57 [0.44-0.84] vs. (0.14 [0.11-0.19], P < 0.01). The number of specific [(125)I]alpha-bungarotoxin binding sites to junctional nicotinic acetylcholine receptors was higher in the diaphragm than in the EDL (1.15 fmol/mg [0.48-1.70] vs. 0.55 fmol/mg [0.23-0.70 ], P < 0.05). Conclusion The current study indicates that the resistance of the diaphragm to neuromuscular blocking agents can be explained by both a higher mean quantal content of endplate potentials and a higher number of nicotinic acetylcholine receptor binding sites than in the peripheral EDL muscle.

Effect of 1,1-dimethylphenyl 1,4-piperazinium on mouse tracheal smooth muscle responsiveness

2005 ◽  
Vol 288 (6) ◽  
pp. L1139-L1145 ◽  
Author(s):  
G. Dorion ◽  
E. Israël-Assayag ◽  
M. J. Beaulieu ◽  
Y. Cormier
Keyword(s):  
Smooth Muscle ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Bronchial Hyperresponsiveness ◽  
Smooth Muscles ◽  
Inhibitory Effect ◽  
Tracheal Smooth Muscle ◽  
In Vivo Model ◽  
Airway Response

Bronchial hyperresponsiveness is one of the main features of asthma. A nicotinic receptor agonist, 1,1-dimethylphenyl 1,4-piperazinium (DMPP), has been shown to have an inhibitory effect on airway response to methacholine in an in vivo model of asthma. The aims of this study were to 1) verify whether nicotinic acetylcholine receptors (nAChR) were present on mouse tracheal smooth muscle, 2) verify whether bronchoprotection observed in mice was due to a direct effect on airway smooth muscle, and 3) compare the effects of nicotinic agonists to that of salbutamol. α3-, α4-, and α7-nAChR subunits were detected by immunofluorescence on tracheal tissues from normal BALB/c mice. The effect of DMPP on tracheal responsiveness was verified by an isometric method. Tracheas were isolated from normal mice, placed in organ baths, and contracted with a single dose of methacholine. Cumulative doses of DMPP or salbutamol were added to the baths. Results show that mouse tracheal smooth muscle is positive for α4- and α7-nAChR subunits and that the epithelium is positive for α3-, α4-, and α7-subunits. DMPP induced a greater dose-dependent relaxation of tracheal smooth muscles precontracted with methacholine than with salbutamol. These results suggest that the smooth muscle-relaxing effect of DMPP could have some interest in the treatment of obstructive pulmonary diseases.

scholarly journals CaMKII Is Involved in the Choline-Induced Downregulation of Acetylcholine Release in Mouse Motor Synapses

Acta Naturae ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 110-113 ◽  
Author(s):  
A. E. Gaydukov ◽  
O. P. Balezina
Keyword(s):  
Protein Kinase ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Inhibitory Effect ◽  
Synaptic Activity ◽  
Ach Release ◽  
Calcium Dependent ◽  
Calcium Calmodulin Dependent ◽  
Kinase C ◽  
Dependent Protein

We investigated the involvement of calcium-dependent enzymes, protein kinase C (PKC) and calcium-calmodulin-dependent protein kinase II (CaMKII), in the signaling pathway triggered by the activation of presynaptic alpha7-type nicotinic acetylcholine receptors by exogenous choline, leading to downregulation of the evoked acetylcholine (ACh) release in mouse motor synapses. Blockade of PKC with chelerythrine neither changed the evoked release of ACh by itself nor prevented the inhibitory effect of choline. The CaMKII blocker KN-62 did not affect synaptic activity but fully prevented the choline-induced downregulation of ACh release.

scholarly journals Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release

2020 ◽  
Vol 9 (9) ◽  
pp. 2887
Author(s):  
Katrin Richter ◽  
Raymond Ogiemwonyi-Schaefer ◽  
Sigrid Wilker ◽  
Anna I. Chaveiro ◽  
Alisa Agné ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Mononuclear Leukocytes ◽  
Amyloid Β Peptide ◽  
Monocytic Cells ◽  
Cholinergic Mechanism ◽  
Beta Peptide ◽  
Α7 Nicotinic Acetylcholine Receptors

Amyloid-β peptide (Aβ1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of the nervous system. Known interaction partners of Aβ1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aβ1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1β by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aβ1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aβ1-42. IL-1β concentrations were measured in the supernatant. Aβ1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1β-release by monocytic cells, whereas reverse Aβ42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aβ1-42 function that enables monocytic IL-1β release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aβ1-42 in the context of sterile systemic inflammation.

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