The patient with acute neurological problems
Ian Peate, Helen Dutton in Acute Nursing Care, 2014
Once the synapse has occurred the neurotransmitter must be cleared from the synaptic cleft, otherwise the post-synaptic cell will be stimulated repeatedly. Neuro-transmitters can be cleared in three ways: Enzyme inactivation – enzymes break down the molecular structure of the neurotransmitter, e.g. acetylcholine is inactivated by acetylcholinesterase.Cellular uptake – neurotransmitters are transported back to the neurone that released them and reused, e.g. norepinephrine (noradrenaline), or taken up by glial cells.Diffusion – neurotransmitters diffuse away from the synaptic cleft preventing contact with their receptor sites. Neurones receive thousands of synapses. Weak synapses do not generate action potentials: if the signal is strong enough an action potential will occur and an impulse will be transmitted. This is described as an ‘all or nothing’ event.
The autonomic nervous system
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its component choline and acetate. It is one of the fastest acting enzymes in the body, and acetylcholine removal occurs in less than 1 ms. The most important mechanism for the removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic postganglionic neuron that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines, epinephrine and norepinephrine, are inactivated by catechol-O-methyltransferase (COMT) in the liver. Of lesser importance in terms of the termination of neurotransmitter activity, is the diffusion of the neurotransmitter away from the synapse. The neurotransmitter is then eliminated by extraneuronal sites.
Medical Management of Chemical Warfare Agents
Brian J. Lukey, James A. Romano, Salem Harry in Chemical Warfare Agents, 2019
Three cholinesterases exist within the human body. The first is acetylcholinesterase (AChE), also known as true cholinesterase, red cell cholinesterase, or whole blood cholinesterase. Acetylcholinesterase normally hydrolyzes acetylcholine to acetic acid and choline. While AChE is in the cells of all body organs, the amount of AChE in the cells of each organ varies in concentration. One type of cell particularly rich in AChE is the red blood cell. The AChE found at nerve endings is anchored to the plasma membrane through a glycolipid (King, 2006), and this cholinesterase is often referred to as tissue cholinesterase. The other human cholinesterases are butyrylcholinesterase (BuChE), also known as plasma cholinesterase or pseudocholinesterase, and carboxylesterase (CaE). The concentrations of each of these vary from organ to organ. In the human, CaE is only contained within cells, not within plasma, as is found in other animal species. All three of these cholinesterases combine with nerve agents and are inhibited by them. Pharmacologists are hoping in the future to be able to employ both BuChE and CaE as bioscavengers of NA, thus decreasing the amount of nerve agent reaching the active sites of AChE.
Neurotoxic responses of rainbow trout (Oncorhynchus mykiss) exposed to fipronil: multi-biomarker approach to illuminate the mechanism in brain
Published in Drug and Chemical Toxicology, 2022
Arzu Uçar, Fatma Betül Özgeriş, Veysel Parlak, Aslı Çilingir Yeltekin, Esat Mahmut Kocaman, Gonca Alak, Muhammed Atamanalp
Acetylcholinesterase is a hydrolase enzyme, predominantly found in muscle tissue and the nervous system of organisms. It acts an important role in the neurotransmission and widely used enzyme in the determination of the neurotoxic effects of xenobiotics in the aquatic ecosystem (Kim and Lee 2018). The research have shown that Acetylcholinesterase (AChE) activity is blockaged by metals, pesticides, pharmaceuticals and other pollutants in aquatic medium (Rhee et al.2013, Ezeoyili et al.2019), and at pesticides exposed organisms AChE activity acts as a neurotoxicity indicator (Amiard-Triquet 2009). Pesticides have a very specific mode of action that inhibits cholinesterase enzyme (ChE) activity in the nervous system. This makes it important to determine AChE activity in toxicity tests (Sandoval-Herrera et al.2019).
In vitro P-glycoprotein activity does not completely explain in vivo efficacy of novel centrally effective oxime acetylcholinesterase reactivators
Published in Drug and Chemical Toxicology, 2019
Mary Beth Dail, Edward Caldwell Meek, Howard Wayne Chambers, Janice Elaine Chambers
The organophosphate (OP) anticholinesterase class includes both insecticides (e.g., chlorpyrifos, diazinon, malathion) and the nerve agents (e.g., sarin, VX, tabun). Since these chemicals persistently inhibit acetylcholinesterase (AChE), excess acetylcholine accumulates in synapses resulting in excitotoxicity, seizures, permanent brain damage, and even death. Because of the large quantities of OPs present worldwide, they pose a great chemical threat. The OP nerve agent, sarin, was manufactured by a cult named ‘Aum Supreme Truth’ and released in 1994 near the district court in Matsumoto and in 1995 in the subway near the National Police Agency in Tokyo (Yanagisawa et al.2006) in terrorist attacks that resulted in 19 deaths and 6100 exposures. More recently, the Assad regime deployed sarin in Syria in 2013 and 2017 resulting in many civilian deaths (Loveluck 2017). VX was used to assassinate the half-brother of North Korean leader Kim Jong Un (Swenson 2017) and Novichok, which is thought to be a new and extremely toxic OP nerve agent, was used in the 4 March 2018 attempted assassination of a former Russian spy and his daughter (Hay 2018). OP insecticide poisoning has killed 5 million people during the last 30 years and continues to kill at the rate of 200,000 per year, mostly by deliberate ingestion during suicide attempts (Eddleston and Chowdhury 2015). Because of such risks, therapies to counteract OP poisoning effects, both physiologic and cognitive, continue to be of paramount importance.
Acute and sublethal effects of organophosphate insecticide chlorpyrifos on freshwater fish Oreochromis niloticus
Published in Drug and Chemical Toxicology, 2019
Rajib Majumder, Anilava Kaviraj
Reduction in acetylcholinesterase activity in hepatic tissues of O. niloticus due to chlorpyrifos exposure observed in the present study bear similarity with the findings of previous workers studying the same in different fish tissues viz. brain of Gambusia affinis (Rao et al.2005), brain, gill (Rao et al.2003), and gonad (Oruç 2010) of O. niloticus, brain of Tandanus tandanus (Huynh and Nugegoda 2012), liver of Chanos chanos (Palanikumar et al. 2014), brain of Anabas testudineus (Tam et al. 2015), and brain of Rainbow trout (Topal et al. 2016) exposed to chlorpyrifos. Chlorpyrifos like other organophosphate insecticides can disrupt the activities of acetylcholinesterase by irreversible binding to its serine hydroxyl group and thus inactivate the enzyme (Oruç 2010). Acetylcholinesterase inhibition in neuromuscular junctions and cholinergic synapses induces accumulation of acetylcholine, which finally leads to disturbances related to nerve impulse propagation and interferes energy metabolism in the nervous system (Thompson and Richardson 2004, Da Cuna et al. 2011).
Related Knowledge Centers
- Catalysis
- Chemical Synapse
- Choline
- Cholinesterase
- Enzyme
- Neuromuscular Junction
- Neurotransmission
- Neurotransmitter
- Acetylcholine
- Cholinergic