Acetylcholine modulates the virulence of and regulates an appropriate immune response to infection in a infection model. Indeed, the evidence suggests that possesses a functional cholinergic receptor that can regulate filamentous growth and biofilm formation. Furthermore, immune cell subsets possess repertories of cholinergic receptors which regulate an effective and appropriate cellular immune response to infection. This study aimed to investigate the cholinergic receptor subtype involved in regulation of filamentous growth and biofilm formation by and determine the roles of cholinergic receptors in modulation of immune cell subsets. The general muscarinic receptor agonist, pilocarpine hydrochloride, inhibited biofilm formation and pathogenicity, a phenomenon that could be reversed using the general muscarinic receptor antagonist, scopolamine. Pilocarpine hydrochloride protected larvae from infection via inhibition of filamentation and appropriate regulation of cellular immunity. However, scopolamine abrogated the capacity of pilocarpine hydrochloride to protect larvae from infection. Furthermore, acetylcholine and pilocarpine hydrochloride exhibited differential modulatory capabilities on hemocyte responses to The data in this article demonstrate that a muscarinic receptor modulates filamentation and biofilm formation. Furthermore, the results suggest that hemocyte subsets possess unique repertoires of cholinergic receptors that regulate their differentiation, activation, and function in contrasting manners. Therefore, targeting cholinergic receptors by repurposing currently licensed cholinergic drugs may offer novel therapeutic solutions for the prevention or treatment of fungal infections. is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. infections are combatted by the host immune system. However, triggers a strong inflammatory response that, if not appropriately regulated, can damage host tissues. Therefore, it is important that the host immune response eliminates the fungus but limits tissue damage. This study provides evidence that targeting cholinergic receptors cannot only curb the virulence of by inhibiting filamentous growth and biofilm formation but can also appropriately regulate the host immune response to induce rapid clearance with limited damage to vital tissues. This article provides evidence that repurposing licensed drugs that target cholinergic receptors may offer novel therapeutic solutions for the prevention or treatment of fungal infections.
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http://dx.doi.org/10.1128/mSphere.00689-18 | DOI Listing |
Neurol Int
December 2024
Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), São Bernardo do Campo 09606-070, Brazil.
Background/objectives: Antipsychotic medicines are used to treat several psychological disorders and some symptoms caused by dementia and schizophrenia. Haloperidol (Hal) is a typical antipsychotic usually used to treat psychosis; however, its use causes motor or extrapyramidal symptoms (EPS) such as catalepsy. Hal blocks the function of presynaptic D2 receptors on cholinergic interneurons, leading to the release of acetylcholine (ACh), which is hydrolyzed by the enzyme acetylcholinesterase (AChE).
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Univ Angers, INSERM, CNRS, MITOVASC, Équipe CARME, SFR ICAT, F-49000 Angers, France.
Chronic elevated blood pressure impinges on the functioning of multiple organs and therefore harms body homeostasis. Elucidating the protective mechanisms whereby the organism copes with sustained or repetitive blood pressure rises is therefore a topical challenge. Here we address this issue in the adrenal medulla, the master neuroendocrine tissue involved in the secretion of catecholamines, influential hormones in blood pressure regulation.
View Article and Find Full Text PDFBMC Anesthesiol
December 2024
Department of Anesthesiology and Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330001, China.
Objective: This study aimed to observe the impact of Tthoracic paravertebral nerve blockade(TPVB) at left T7 level on the α7nAChR-dependent cholinergic anti-inflammatory pathway in patients undergoing thoracoscopic lobectomy.
Methods: Scheduled thoracoscopic lung surgery patients at the First Affiliated Hospital of Nanchang University from August to September 2023 were divided into two groups according to the surgical site. The experimental group underwent left T7 paravertebral nerve blockade (LTPVB group), while the control group underwent right T7 paravertebral nerve blockade (RTPVB group).
ACS Chem Neurosci
December 2024
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Co-use of xylazine with opioids is a major health threat in the United States. However, a critical knowledge gap exists in the understanding of xylazine-induced pharmacological and pathological impact. Xylazine is mostly known as an agonist of α2-adrenergic receptors (α2-ARs), but its deleterious effects on humans cannot be fully reversed by the α2-AR antagonists, suggesting the possibility that xylazine targets receptors other than α2-ARs.
View Article and Find Full Text PDFJ Mol Neurosci
December 2024
Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.
Elevated inflammatory reactions are a significant component in cerebral ischemia-reperfusion injury (CIRI). Activation of α7-Nicotinic Acetylcholine Receptor (α7nAChR) reduces stroke-induced inflammation in rats, but the anti-inflammatory pathway in microglia under CIRI condition remains unclear. This study employed qRT-PCR, protein assays, NanoString analysis, and bioinformatics to examine the effects of PNU282987 treatment (α7nAChR agonist) on BV2 microglial functional differentiation in oxygen-glucose deprivation/reoxygenation (OGDR) condition.
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