scholarly journals Colocalization of ATP and nicotinic ACh receptors in the identified vagal preganglionic neurone of rat.

1995 ◽  
Vol 489 (2) ◽  
pp. 519-527 ◽  
Author(s):  
J Nabekura ◽  
S Ueno ◽  
T Ogawa ◽  
N Akaike
Keyword(s):  
Preganglionic Neurone ◽  
Ach Receptors

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

scholarly journals Acetylcholine Receptors

1972 ◽  
Vol 60 (3) ◽  
pp. 248-262 ◽  
Author(s):  
H. Criss Hartzell ◽  
Douglas M. Fambrough
Keyword(s):  
Acetylcholine Receptors ◽  
Time Course ◽  
Plasma Membranes ◽  
Scintillation Counting ◽  
Receptor Density ◽  
Rat Diaphragm ◽  
Leg Muscles ◽  
And Function ◽  
Quantitative Radioautography ◽  
Ach Receptors

Using 125iodine-labeled α-bungarotoxin (α-BGT-125I) and quantitative radioautography, we have studied the time-course of the change in acetylcholine (ACh) receptor distribution and density occurring in rat diaphragm after denervation. In innervated fibers, ACh receptors are localized at the neuromuscular junction and the extrajunctional receptor density is less than five receptors per square micrometer. The extrajunctional receptor density begins to increase between 2 and 3 days after denervation and increases approximately linearly to 1695 receptors/µm2 at 14 days, subsequently decreasing to 529 receptors/µm2 at 45 days. We have isolated plasma membranes from rat leg muscles at various times after denervation and find that the change in concentration of ACh receptors in the membranes measured by α-BGT-125I binding and scintillation counting follows a time-course similar to the change in ACh receptor density measured radioautographically. Furthermore, we have correlated extrajunctional ACh receptor density measured by radioautography with extrajunctional ACh sensitivity measured by iontophoretic application of ACh and intracellular recording and find that the log of ACh receptor density is related to 0.53 times the log of ACh sensitivity. These results are discussed in terms of the electrophysiological experiments on the ACh receptor and the recent, more biochemical approaches to the study of ACh receptor control and function.

Some properties of acetylcholine receptors in human cultured myotubes

1985 ◽  
Vol 224 (1235) ◽  
pp. 183-196 ◽  
Keyword(s):  
Acetylcholine Receptors ◽  
Single Channel ◽  
Fold Increase ◽  
Resting Potential ◽  
Patch Clamp Technique ◽  
Membrane Hyperpolarization ◽  
Human Myotubes ◽  
Cultured Myotubes ◽  
Channel Open Time ◽  
Ach Receptors

The distribution and single channel properties of acetylcholine (ACh) receptors in human myotubes grown in tissue culture have been examined. Radioautography of myotubes labelled with [ 125 I]α-bungarotoxin showed that ACh receptors are distributed uniformly over the myotube surface at a density of 3.9 ± 0.5 receptors per square micrometre. Ac­cumulations of ACh receptors (hot spots) were found rarely. The conductance and kinetics of ACh-activated channels were investi­gated with the patch-clamp technique. Cell-attached membrane patches were used in all experiments. A single channel conductance in the range 40–45 pS was calculated. No sublevels of conductance (substates) of the activated channel were observed. The distribution of channel open-times varied with ACh concentration. With 100 nM ACh, the distribution was best fitted by the sum of two exponentials, whereas with 1 μM ACh a single exponential could be fitted. The mean channel open-time at the myotube resting potential (ca. — 70 mV, 22°C) was 8.2 ms. The distribution of channel closed-times was complex at all concentrations of ACh studied (100 nM to 10 μm). With desensitizing doses of ACh (10 μM), channel openings occurred in obvious bursts; each burst usually appeared as part of a ‘cluster’ of bursts. Both burst duration and mean interval between bursts increased with membrane hyperpolarization. Individual channel open-times and burst durations showed similar voltage dependence (e-fold increase per 80 mV hyperpolarization), whereas both the channel closed-times within a burst and the number of openings per burst were independent of membrane potential.

Influence of presynaptic receptors on neuromuscular transmission in rat

1982 ◽  
Vol 242 (5) ◽  
pp. C366-C372 ◽  
Author(s):  
D. F. Wilson
Keyword(s):  
Transmitter Release ◽  
Action Potentials ◽  
Physiological Function ◽  
Motor Nerve ◽  
Presynaptic Receptors ◽  
End Plate ◽  
Feedback Pathway ◽  
Partial Blockade ◽  
Ach Receptors

The presence and physiological significance of acetylcholine (ACh) receptors on motor nerve terminals was examined at the rat diaphragm neuromuscular junction. Intracellular recording techniques were used to monitor end-plate potentials (EPP), miniature end-plate potentials (MEPP), and resting potentials of the muscle fibers. Muscle action potentials were blocked by the cut-muscle technique. Quantal release was determined by the ratio EPP/MEPP, after correcting for nonlinear summation. Blockade of acetylcholinesterase with eserine and neostigmine was tested to determine the influence of residual ACh on transmitter release. Partial blockade of ACh receptors with curare was examined to further clarify the role of these presynaptic receptors. The experiments demonstrate that residual ACh inhibits transmitter release and that blockade of ACh receptors enhances transmitter release. It is concluded that presynaptic ACh receptors exist and that they serve an important physiological function. It is suggested that the presynaptic ACh receptors normally serve to limit transmitter release in a negative feedback pathway.

Cholinergic activation of stridulatory behaviour in the grasshopper Omocestus viridulus (L.)

1997 ◽  
Vol 200 (9) ◽  
pp. 1327-1337 ◽  
Author(s):  
R Heinrich ◽  
B Hedwig ◽  
N Elsner
Keyword(s):  
Rapid Onset ◽  
Suboesophageal Ganglion ◽  
Male And Female ◽  
Ach Receptors ◽  
Cholinergic Activation

When acetylcholine (ACh) and its agonists are injected into neuropile regions of the protocerebrum and the suboesophageal ganglion of male and female grasshoppers of the species Omocestus viridulus (L.), they elicit stridulation in a pattern no different from that of natural song. Stridulation can even be evoked in mated females which normally do not sing. By choosing suitable ACh agonists, nicotinic and muscarinic ACh receptors can be activated selectively. Activation of nicotinic ACh receptors produces individual song sequences with rapid onset; the stridulation induced by activation of the muscarinic ACh receptors begins after a longer latency, increases slowly in intensity and is maintained for many minutes. The sites within the cephalic ganglia where song can be initiated pharmacologically coincide with regions in which descending stridulatory command neurones arborize.

scholarly journals Fulditoxin, representing a new class of dimeric snake toxins, defines novel pharmacology at nicotinic ACh receptors

2020 ◽  
Vol 177 (8) ◽  
pp. 1822-1840 ◽  
Author(s):  
Chun Shin Foo ◽  
Chacko Jobichen ◽  
Varuna Hassan‐Puttaswamy ◽  
Zoltan Dekan ◽  
Han‐Shen Tae ◽  
...  
Keyword(s):  
New Class ◽  
Snake Toxins ◽  
Ach Receptors
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