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Experientia Aug 1959
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Muscarine; Parasympathomimetics
PubMed: 13845452
DOI: 10.1007/BF02158533 -
Brain Research Jan 2010Stimulated vagus nerve excretes acetylcholine into the peripheral immune organs such as the spleen, reducing innate inflammation. Here, we investigated whether...
Stimulated vagus nerve excretes acetylcholine into the peripheral immune organs such as the spleen, reducing innate inflammation. Here, we investigated whether activation of this "cholinergic anti-inflammatory pathway" can be used to reduce cerebral inflammation in a model of hemorrhagic stroke. Experimental intracerebral hemorrhage (ICH) was induced by stereotaxic collagenase injection in rats. Muscarine, an activator of the vagus nerve, or phosphate-buffered saline (control) was injected into the lateral ventricle after induction of ICH. Intraventricular muscarine injection increased heart rate variability in the ICH model, suggesting increased vagus nerve output. Muscarine-injected ICH rats showed improved neurologic outcomes, reduced brain water content, and decreased levels of inflammatory mediators in both brain and spleen. Central muscarine injection was ineffective at reducing cerebral edema without spleen, suggesting that the effect of muscarine is mediated through the vagus nerve-spleen pathway rather than through a direct interaction with the brain. Our results suggest that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself.
Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Brain Edema; Cerebral Hemorrhage; Collagenases; Encephalitis; Inflammation Mediators; Injections, Intraventricular; Male; Muscarine; Muscarinic Agonists; Rats; Rats, Sprague-Dawley; Spleen; Vagus Nerve
PubMed: 19900419
DOI: 10.1016/j.brainres.2009.10.076 -
Journal of Physiology, Paris 1992Postsynaptic Ca2+ changes are involved in control of cellular excitability and induction of synaptic long-term changes. We monitored Ca2+ changes in dendrites and spines... (Review)
Review
Postsynaptic Ca2+ changes are involved in control of cellular excitability and induction of synaptic long-term changes. We monitored Ca2+ changes in dendrites and spines during synaptic and direct stimulation using high resolution microfluorometry of fura-2 injected into CA3 pyramidal neurons in guinea pig hippocampal slice. When driven by current injection from an intracellular electrode or with synaptic stimulation, postsynaptic Ca2+ accumulations were highest in the proximal dendrites with a pronounced fall-off towards the soma and some fall-off towards more distal dendrites. Muscarinic activation by low concentrations of carbachol strongly increased intradendritic Ca2+ accumulation during directly-evoked repetitive firing. This enhancement occurred in large part because muscarinic activation suppressed the normal Ca(2+)-dependent activation of K-channels that mediates adaptation of firing. Repetitive firing of cholinergic fibers in the slice reproduced the effects of carbachol. Inhibition of acetylcholine-esterase activity by eserine enhanced the effects of repetitive stimulation of chlolinergic fibers. All effects were reversible and were blocked by the muscarinic antagonist atropine. Ca2+ accumulations in postsynaptic spines might be the basis of specificity of synaptic plasticity. With selective stimulation of few associative/comissural fibers, Ca2+ accumulated in single postsynaptic spines but not in the parent dendrite. With strong stimulation, dendrite levels also increased but spine levels were considerably higher. The NMDA-receptor antagonist AP-5 blocked Ca(2+)-peaks in spines, but left Ca2+ changes in dendrite shafts largely unaffected. Sustained steep Ca2+ gradients between single spines and the parent dendrite, often lasting several minutes, developed with repeated stimulation. Our results demonstrate a spine entity that can act independent from the dendrite with respect to Ca(2+)-dependent processes. Muscarinic augmentation of dendritic Ca2+ levels might reduce diffusional loss of Ca2+ from hot spines into the parent dendrite, thus supporting cooperativity and associativity of synaptic plasticity.
Topics: Animals; Brain; Calcium; Dendrites; Fluorometry; Guinea Pigs; In Vitro Techniques; Muscarine; Neuronal Plasticity; Neurons; Signal Transduction; Synapses; Synaptic Transmission
PubMed: 1343597
DOI: 10.1016/s0928-4257(05)80008-7 -
Experientia Jul 1953
Topics: Ammonium Compounds; Muscarine; Salts
PubMed: 13095417
DOI: 10.1007/BF02172437 -
Brain Research Sep 1994The effects of muscarine on small, putative C-cells and large, putative B-cells dissociated from bullfrog paravertebral sympathetic ganglia were studied by whole cell...
The effects of muscarine on small, putative C-cells and large, putative B-cells dissociated from bullfrog paravertebral sympathetic ganglia were studied by whole cell and single channel recording techniques. The dominant action of muscarine was to activate an inwardly-rectifying K+ current (IK(G)) in C-cells and to suppress M-current (IM) in B-cells. However, both IM and IK(G) were affected by muscarine in 5 out of 78 putative C-cells and in 8 others only IM was affected. By contrast, IK(G) was only activated in 1 out of 105 B-cells. This predicts that the muscarinic slow IPSP, which can be evoked by preganglionic stimulation, occurs exclusively in C-cells. 6% of these cells could, however, generate a muscarinic slow EPSP in addition to a slow IPSP and 10% could generate a slow EPSP without a slow IPSP. The rectification associated with IK(G) was neither a direct consequence of the direction of movement of K+ ions nor a simple consequence of channel block by intracellular Mg2+ or Na+ ions. The fit of the activation curve by a Boltzmann equation suggests that the conductance underlying IK(G) is controlled by a voltage-dependent gating charge (valency approximately -2). Muscarine activated no new channels in outside-out or cell-attached patches but increased the opening probability of two types of K+ channels (unitary conductances approximately 20 pS and approximately 55 pS). The possible role of these channels in the generation of IK(G) is discussed.
Topics: Animals; Cell Membrane; Cell Size; Electric Conductivity; Ganglia, Sympathetic; Muscarine; Potassium Channels; Rana catesbeiana
PubMed: 7834347
DOI: 10.1016/s0006-8993(09)90031-2 -
British Journal of Pharmacology 19801 From measurements of the affinity constants of hydratropyltropine and its methiodide for muscarine-sensitive acetylcholine receptors in the guinea-pig ileum, the...
1 From measurements of the affinity constants of hydratropyltropine and its methiodide for muscarine-sensitive acetylcholine receptors in the guinea-pig ileum, the increment in log K for the hydroxyl group in atropine is 2.06 and in the methiodide it is 2.16. These effects are slightly bigger than any so far recorded with these receptors. 2 The estimate of the increment in apparent molal volume for the hydroxyl group is 1.1 cm3/mol in atropine and 1.0 cm3/mol in the methobromide. 3 The large effect of the group on affinity may be linked to its small apparent size in water as suggested in the previous paper.
Topics: Animals; Atropine; Guinea Pigs; Hydroxylation; In Vitro Techniques; Kinetics; Muscarine; Muscle Contraction; Muscle, Smooth; Receptors, Cholinergic
PubMed: 7470742
DOI: 10.1111/j.1476-5381.1980.tb10905.x -
Anesthesie Et Analgesie Dec 1953
Topics: Humans; Muscarine; Succinylcholine
PubMed: 15444511
DOI: No ID Found -
The Journal of Neuroscience : the... Jul 1996Submembrane [Ca2+]i changes were examined in rat chromaffin cells by monitoring the activity of an endogenous Ca(2+)-dependent protein: the large conductance Ca(2+)-and...
Submembrane [Ca2+]i changes were examined in rat chromaffin cells by monitoring the activity of an endogenous Ca(2+)-dependent protein: the large conductance Ca(2+)-and voltage-activated K+ channel (also known as the BK channel). The Ca2+ and voltage dependence of BK current inactivation and conductance were calibrated first by using defined [Ca2+]i salines. This information was used to examine submembrane [Ca2+]i elevations arising out of Ca2+ influx and muscarine-mediated release of Ca2+ from intracellular stores. During Ca2+ influx, some BK channels are exposed to [Ca2+]i of at least 60 microM. However, the distribution of this [Ca2+]i elevation is highly nonuniform so that the average [Ca2+]i detected when all BK channels are activated is only approximately 10 microM. Intracellular dialysis with 1 mM or higher EGTA spares only the BK channels activated by the highest [Ca2+]i during influx, whereas dialysis with 1 mM or higher BAPTA blocks activation of all BK channels. Submembrane [Ca2+]i elevations fall rapidly after termination of short (5 msec) Ca2+ influx steps but persist above 1 microM for several hundred milliseconds after termination of long (200 msec) influx steps. In contrast to influx, the submembrane [Ca2+]i elevations produced by release of intracellular Ca2+ by muscarinic actetylcholine receptor (mAChR) activation are much more uniform and reach peak levels of 3-5 microM. Our results suggest that during normal action potential activity only 10-20% of BK channels in each chromaffin cell see sufficient [Ca2+]i to be activated.
Topics: Animals; Calcium; Cells, Cultured; Chromaffin System; Dose-Response Relationship, Drug; Membrane Potentials; Muscarine; Potassium Channels; Rats
PubMed: 8699245
DOI: 10.1523/JNEUROSCI.16-14-04344.1996 -
Toxicology and Applied Pharmacology Jan 1978
Topics: Animals; Choline O-Acetyltransferase; Cholinesterase Inhibitors; Female; Furans; Lethal Dose 50; Male; Mice; Muscarine; Rats; Respiration; Respiration, Artificial
PubMed: 625765
DOI: 10.1016/s0041-008x(78)80033-7 -
Journal of Neural Transmission 1985We reviewed recent evidence that chemical kindling of epileptic seizures can be induced by injection into the amygdala of multiple cholinergic muscarinic agonists, and... (Review)
Review
We reviewed recent evidence that chemical kindling of epileptic seizures can be induced by injection into the amygdala of multiple cholinergic muscarinic agonists, and blocked by multiple muscarinic antagonists. The stereospecific induction of kindling by (+) but not by (-) acetyl-beta-methylcholine shows that some types of repeated synaptic activation can produce epilepsy, in the absence of specific brain damage. The failure of bicuculline (but not of carbachol) to produce kindling with amygdaloid injections, and its ability to produce a limited seizure spread in neocortex, suggest that repetitive seizure activity alone is not sufficient to produce kindling. A review of some recent neurochemical changes in the synaptic apparatus associated with some types of kindling suggests potential areas for future investigation, but no cause-and-effect relationship between neurochemical and behavioral changes can be inferred so far.
Topics: Amygdala; Animals; Brain Damage, Chronic; Carbachol; Epilepsy; Hippocampus; Humans; Kindling, Neurologic; Muscarine; Neural Pathways; Parasympathetic Nervous System; Rats; Seizures
PubMed: 3900291
DOI: 10.1007/BF01252612