scholarly journals The Regulation Effect of α7nAChRs and M1AChRs on Inflammation and Immunity in Sepsis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Song Hu ◽  
Yundong Wang ◽  
Hongbing Li

The inflammatory storm in the early stage and immunosuppression in the late stage are responsible for the high mortality rates and multiple organ dysfunction in sepsis. In recent years, studies have found that the body’s cholinergic system can spontaneously and dynamically regulate inflammation and immunity in sepsis according to the needs of the body. Firstly, the vagus nerve senses and regulates local or systemic inflammation by means of the Cholinergic Anti-inflammatory Pathway (CAP) and activation of α7-nicotinic acetylcholine receptors (α7nAChRs); thus, α7nAChRs play important roles for the central nervous system (CNS) to modulate peripheral inflammation; secondly, the activation of muscarinic acetylcholine receptors 1 (M1AChRs) in the forebrain can affect the neurons of the Medullary Visceral Zone (MVZ), the core of CAP, to regulate systemic inflammation and immunity. Based on the critical role of these two cholinergic receptor systems in sepsis, it is necessary to collect and analyze the related findings in recent years to provide ideas for further research studies and clinical applications. By consulting the related literature, we draw some conclusions: MVZ is the primary center for the nervous system to regulate inflammation and immunity. It coordinates not only the sympathetic system and vagus system but also the autonomic nervous system and neuroendocrine system to regulate inflammation and immunity; α7nAChRs are widely expressed in immune cells, neurons, and muscle cells; the activation of α7nAChRs can suppress local and systemic inflammation; the expression of α7nAChRs represents the acute or chronic inflammatory state to a certain extent; M1AChRs are mainly expressed in the advanced centers of the brain and regulate systemic inflammation; neuroinflammation of the MVZ, hypothalamus, and forebrain induced by sepsis not only leads to their dysfunctions but also underlies the regulatory dysfunction on systemic inflammation and immunity. Correcting the neuroinflammation of these regulatory centers and adjusting the function of α7nAChRs and M1AChRs may be two key strategies for the treatment of sepsis in the future.

2021 ◽  
Author(s):  
Noemi D. Paguigan ◽  
Jortan O. Tun ◽  
Lee S. Leavitt ◽  
Zhenjian Lin ◽  
Kevin Chase ◽  
...  

In our efforts to discover new drugs to treat pain, we identified molleamines A-E (1-5) as major neuroactive components of the sea slug, Pleurobranchus forskalii and their prey, Didemnum molle tunicates. The chemical structures of molleamines were elucidated by spectroscopy and confirmed by the total synthesis of molleamines A (1) and C (3). Synthetic 3 completely blocked acetylcholine-induced calcium flux in peptidergic nociceptors (PNs) in the somatosensory nervous system. Compound 3 affected neither the α7 nAChR nor the muscarinic acetylcholine receptors in calcium flux assays. In addition to nociceptors, 3 partially blocked the acetylcholine-induced calcium flux in the sympathetic nervous system, including neurons from the superior cervical ganglion. Electrophysiology revealed a block of α3β4 (mouse) and α6/α3β4 (rat) nicotinic acetylcholine receptors (nAChRs), with IC50 values of 1.4 and 3.1 μM, respectively. Molleamine C (3) is a partial antagonist, reaching a maximum block of 76-82% of the acetylcholine signal and showing no partial agonist response. Molleamine C (3) may thus provide a lead compound for the development of neuroactive compounds with unique biological properties.


1997 ◽  
Vol 200 (21) ◽  
pp. 2685-2692 ◽  
Author(s):  
S Buckingham ◽  
B Lapied ◽  
H Corronc ◽  
F Sattelle

The neonicotinoid insecticide Imidacloprid acts at three pharmacologically distinct acetylcholine receptor (AChR) subtypes in the cockroach (Periplaneta americana) nervous system, but is ineffective on muscarinic receptors. Imidacloprid (3-100µmoll-1) induced dose-dependent depolarizations at cockroach cercal afferent/giant interneurone synapses. These responses were insensitive to 20µmoll-1 atropine but were completely blocked by the nicotinic antagonist mecamylamine (50µmoll-1). Similarly, Imidacloprid-induced depolarizations of cultured cockroach dorsal unpaired median (DUM) neurones dissociated from the same (terminal abdominal) ganglion were also completely blocked by 100µmoll-1 mecamylamine. However, two components of the response could be distinguished on the basis of their differential sensitivities to 0.1µmoll-1-bungarotoxin (-BTX), which selectively blocks AChRs with 'mixed' nicotinic/muscarinic pharmacology in this preparation. This indicates that Imidacloprid affects both AChRs sensitive to -BTX and -BTX-insensitive nicotinic acetylcholine receptors (nAChRs). Thus, in the cockroach, Imidacloprid activates -BTX-sensitive synaptic nAChRs in giant interneurones, -BTX-insensitive extrasynaptic nAChRs in DUM neurones, and a recently characterized DUM neurone 'mixed' AChR that is sensitive to both nicotinic and muscarinic ligands. Imidacloprid does not act on muscarinic acetylcholine receptors (mAChRs) present on DUM neurone cell bodies and at the cercal afferent/giant interneurone synapses. This study shows that Imidacloprid can act on pharmacologically diverse nAChR subtypes.


2020 ◽  
Vol 18 ◽  
Author(s):  
Jielin Deng ◽  
Hong Jiang

: Nicotinic acetylcholine receptors (nAChRs) comprise a large family of ligand-gated ion channels that have a broad distribution in neurons and non-neuronal cells throughout the body. Native nAChRs, activated by acetylcholine (ACh) endogenously, are involved in a variety of physiological and pathophysiological processes. They regulate processes necessary for network operations through neurotransmitter release, cell excitability and neuronal integration. Emerging evidence suggests that nAChRs are capable of regulating cardiovascular (CV) functions in a cell type-specific manner, through the nervous system and non-neuronal tissues. The aim of this review is to describe the most recent findings regarding the role of nAChRs inside and outside the nervous system in the regulation of CV activities.


2021 ◽  
Author(s):  
Joanne Figueiredo ◽  
Joshua Rest ◽  
Sarah Adamo ◽  
Rebecca Grella ◽  
James Dilger

Abstract Nicotinic acetylcholine receptors (nAChRs) play a pivotal role in the nervous system, and there is great interest in understanding their evolution. Cnidarians, an ancestral group of metazoans, display an early nervous system utilizing complex neural architecture that provides insight into the early evolution and function of nAChRs. Using the anthozoan Nematostella vectensis, we found that the rate of peristalsis, a radial constriction of the body column, is modulated by nicotinic agonists. Nicotine caused a robust, dose dependent increase in the rate of peristalsis. The peristalsis rate also increased in response to ACh in the presence of edrophonium, an acetylcholine esterase inhibitor. Thus, N. vectensis possesses functional nAChRs. We developed a phylogeny of nAChRs from 15 cnidarian and 16 bilaterian species. Our results indicate that the large number of cnidarian and bilaterian nAChR gene copies is convergent, resulting from gene expansions after the two lineages diverged. These independent expansions led to an average of 31 and 34 paralogous nAChR gene copies in sampled bilaterians and cnidarians, respectively. The N. vectensis proteome contains 49 paralogous nAChR copies. The independent expansions indicate that nAChRs receptors in cnidarians may have distinct pharmacological and biochemical characteristics in comparison to their bilaterian counterparts.


Author(s):  
C. Welzl ◽  
A.L. Leisewitz ◽  
L.S. Jacobson ◽  
T. Vaughan-Scott ◽  
E. Myburgh

This study was designed to document the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retro-spectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are manysimilarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.


2021 ◽  
Vol 10 (2) ◽  
pp. 29-43
Author(s):  
Rohit Rastogi ◽  
Mamta Saxena ◽  
Devendra K. Chaturvedi ◽  
Mayank Gupta ◽  
Akshit Rajan Rastogi ◽  
...  

Our entire body, including the brain and nervous system, works with the help of various kinds of biological stuff which includes positively charged ions of elements like sodium, potassium, and calcium. The different body parts have different energy levels, and by measuring the energy level, we can also measure the fitness of an individual. Moreover, this energy and fitness are directly related to mental health and the signals being transmitted between the brain and other parts of the body. Various activities like walking, talking, eating, and thinking are performed with the help of these transmission signals. Another critical role played by them is that it helps in examining the mechanisms of cells present at various places in the human body and signaling the nervous system and brain if they are properly functioning or not. This manuscript is divided into two parts where, in the first part, it provides the introduction, background, and extensive literature survey on Kirlian experiments to measure the human's organ energy.


1993 ◽  
Vol 175 (1) ◽  
pp. 305-311
Author(s):  
H. Le Corronc ◽  
B. Hue

Biochemical studies of the central nervous system (CNS) of locusts (Breer and Knipper, 1984; Knipper and Breer, 1988) have provided evidence for a muscarinic negative feedback mechanism in which muscarinic antagonists and agonists, respectively, enhance and decrease the acetylcholine (ACh) output. More recently, this inhibitory action of presynaptic muscarinic acetylcholine receptors (mAChrs) has been demonstrated in cockroach (Hue et al. 1989; Le Corronc et al. 1991) and in tobacco hornworm (Trimmer and Weeks, 1989) using electrophysiological methods. However, in insects, most experiments have not been performed under physiological conditions but in the presence of acetylcholinesterase inhibitors or exogenous agonists. The aim of this study was to determine whether the release of ACh at a central synapse in the cockroach, Periplaneta americana, could be modulated by endogenous ACh acting on presynaptic muscarinic receptors.


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