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Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
It is essential for proper synaptic action that the neurotransmitter binds to the postsynaptic receptor for a relatively short interval. Otherwise, the synapse becomes inoperative, as the neurotransmitter remains bound to the receptor. ACh is hydrolyzed by the enzyme AChE, as in the NMJ (Section 5.2). In the case of other neurotransmitters, the neurotransmitter concentration in the cleft rapidly decreases, which unbinds the neurotransmitter from the receptor. This decrease is mainly due to uptake by transporters that are specific for each neurotransmitter and which are driven by the electrochemical potential gradient of Na+. In the case of ACh, only choline is transported back into the presynaptic terminal, as in the NMJ (Section 5.2). Dopamine, norepinephrine, serotonin, most of GABA and glycine, and some of the glutamate are transported back directly into the presynaptic terminal. Some of GABA and glycine and most of the glutamate are transported into glial cells, where GABA and glutamate are converted to glutamine that is transported back to the presynaptic terminal. Glial cells can also synthesize, store, and release neurotransmitters and can also have receptors for neurotransmitters that modulate their function. The action of neuropeptides is terminated by peptidases, which are extracellular enzymes that break the neuropeptides into inactive amino acids.
Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
In this chapter, the authors described biosynthesis, storage, release, receptor activation, and inactivation of important neurotransmitters. Various neuromodulators are described as opioid and non-opioid peptides. It has been observed that vasopressin and oxytocin play an important role as neurohormones while second messengers like cAMP, cGMP, DAG, IP3, and calcium facilitate the responses of neurotransmitters at their postsynaptic receptors. Throughout the chapter, it was evident that some neurotransmitters like adrenaline also work as neurohormone. Adenosine and ATP act as transmitters and/or modulators in the CNS. NO also acts as a neurotransmitter and neuromodulator in the CNS. Thus, it can be concluded that it is very complex to clearly delineate the role of neurotransmitters, neuromodulators, and neurohormones. However, imbalance of these neurochemicals is one of the major pathological events in genesis of various CNS disorders like AD, PD, psychosis, and depression. It is also evident that drugs used in management of such neuropsychiatric disorders mainly target on correcting the neurochemical imbalance.
Muscle
Published in Sarah Armstrong, Barry Clifton, Lionel Davis, Primary FRCA in a Box, 2019
Sarah Armstrong, Barry Clifton, Lionel Davis
Disorders in postsynaptic receptors Myasthenia gravisImmune mediated, neonatal, congenital or drug inducedMost are due to immune-mediated IgG attack on post-synaptic receptors (may involve presynaptic receptors) causing reduction in receptor densityMuscle weakness – especially ocular, bulbar (high risk of aspiration), respiratory and limbTreament – anticholinesterase inhibitors (e.g. pyridostigmine), immunosuppression, IvIG and plasmapheresis in severe casesIncreased sensitivity to NMBDs and relative resistance to suxamethonium
AChE mRNA expression as a possible novel biomarker for the diagnosis of coronary artery disease and Alzheimer’s disease, and its association with oxidative stress
Published in Archives of Physiology and Biochemistry, 2022
The AChE plays an important role in cholinergic metabolism by hydrolysing neurotransmitter acetylcholine (ACh) in cholinergic synapse (Aslan et al.2019, Türkeş et al.2019). Most of the ACh molecules released into the synaptic space bind to postsynaptic receptors. ACh molecules not bound to receptors are hydrolysed by AChE. According to the cholinergic hypothesis, there is a metabolic relationship between AD and CAD. The AChE, a cholinergic biomarker, also has an effect on coronary artery disease (CAD) as it hydrolyses ACh that provides flexibility within the blood vessels (Collins et al.1995). Endothelium-derived relaxing factor (EDRF), providing flexibility within the vessel, is provided by the vascular endothelium (Yanagisawa et al.1988, Rubanyi 1991). The EDRF is released by a number of physico-chemical stimuli, including ACh and endogenous hormones. The ACh stimulates endothelium-dependent relaxation in monkey, dog, rabbit, and human with CAD (Collins et al.1993).
Expression of ADR-α1, 2 and ADR-β2 in cumulus cell culture of infertile women with polycystic ovary syndrome and poor responder who are a candidate for IVF: the novel strategic role of clonidine in this expression
Published in Journal of Receptors and Signal Transduction, 2021
Farideh Zafari Zangeneh, Maryam Bagheri, Maryam Sarmast Shoushtari, Mohammad Mehdi Naghizadeh
In the central, paraventricular nucleus (PVN) of the hypothalamus is a responder for stress which contains hypophysiotrophic PVN neurons that can directly control the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis [58]. The alpha1-receptor subtype-specific mRNA expressions and the expression of its binding sites have been designated in PVN in stress-induced activation of the HPA axis [51]. The sensitized response of the HPA axis for the exposure of the chronic intermittent cold stress can be attributed to an intensity response of α1-adrenoceptor activation in the PVN. This increase response could be assumed to be the results of an elevation in postsynaptic receptor number and its affinity, or facilitation in the transduction of receptor-activated signal. Chronic intermittent cold stress can produce an up-regulation of α1-adrenoceptor in the postsynaptic position [59,60]. This is a central response and it should be noted that the HPA axis and SNS activities are higher in PCO than normal. But in peripheral, Kagitani et al (2008) showed that estradiol secretion rate during SON electrical stimulation was significantly decreased by 47 ± 6% but had no effect on the ovarian plexus nerve (OPN). They suggested that SNS projection in the ovary via the SON must be an inhibitory role in the secretion of ovarian estradiol and can be decreased ovarian estradiol [45,46]. This decreasing of estradiol levels probably does not allow the PCO rat modeling to be successful in a previous study [57].
Use of quantitative clinical pharmacology to improve early clinical development success in neurodegenerative diseases
Published in Expert Review of Clinical Pharmacology, 2018
Hugo Geerts, Ronald Gieschke, Richard Peck
The effect of drugs on these in silico circuits is implemented in two steps. First, the activity of postsynaptic receptors is calculated using the competition between endogenous neurotransmitter (or substrate) and the active moiety (parent molecule and active metabolites) based on their affinity for that specific receptor and using physiology-based properties of presynaptic firing and autoreceptor feedback. Second, these changes in postsynaptic activity levels are then translated to changes in the conductance of the appropriate voltage-gated ion channels of these specific neuronal cell types, based on published knowledge (for instance D2R couple to A-type K+ channels in Medium Spiny Neurons of the indirect pathway in the striatum). Human pathology is introduced from imaging or postmortem studies and an emergent in silico property of the neuronal network (such as the power spectrum of local field potential oscillations) can be calculated.