The effects exerted by P1 and P2 as well as by A1 and A2 agonists and antagonists purinoceptor on the acute opiate withdrawal induced by morphine were investigated in vitro. Following a 4 min in vitro exposure to morphine, the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. The P1 purinoceptor agonist, adenosine, was able dose-dependently to reduce morphine withdrawal whereas alpha,beta-methylene ATP (APCPP), a P2 purinoceptor agonist, increased morphine withdrawal. Caffeine, a P1 purinoceptor antagonist, was able significantly and in a concentration dependent manner to increase morphine withdrawal whereas quinidine, a P2 receptor antagonist, reduced it. Also, the adenosine A1 receptor agonist, N6-Cyclopentyladenosine (CPA) was able to reduce dose-dependently naloxone-precipitated withdrawal whereas the selective adenosine A(2A) receptor agonist CGS 21680 increased the naloxone-precipitated withdrawal phenomenon. Dipyridamole, a blocker of adenosine reuptake, induced a significant reduction of morphine dependence. Caffeine, an adenosine receptor antagonist, significantly increased the naloxone-precipitated withdrawal effect in a concentration dependent manner. The same effect was observed with 8-phenyltheophylline (8PT), an A1 adenosine receptor antagonist, whereas 3,7-dimethyl-1-propargylxanthine (DMPX), an A2 adenosine receptor antagonist, reduced the naloxone-precipitated withdrawal phenomenon. The results of our experiments indicate that P1 and P2 as well as A1 and A2 purinoceptor agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the purinergic system and opioid withdrawal.
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http://dx.doi.org/10.2174/157488609788173035 | DOI Listing |
J Cheminform
January 2025
School of Systems Biomedical Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, 06978, Seoul, Republic of Korea.
G protein-coupled receptors (GPCRs) play vital roles in various physiological processes, making them attractive drug discovery targets. Meanwhile, deep learning techniques have revolutionized drug discovery by facilitating efficient tools for expediting the identification and optimization of ligands. However, existing models for the GPCRs often focus on single-target or a small subset of GPCRs or employ binary classification, constraining their applicability for high throughput virtual screening.
View Article and Find Full Text PDFMol Med
January 2025
Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, Hubei, China.
Background: Macrophages play an important role in the pathogenesis of ulcerative colitis (UC). We will explore the effects of sodium butyrate (SB) on macrophage function.
Methods: The targets of butyric acid were identified using SwissTargetPrediction database and surface plasmon resonance (SPR).
Cell Biochem Biophys
January 2025
Department of Zoology, University of Allahabad, Prayagraj, Uttar Pradesh, 211002, India.
The present study investigated the role of the neurotensin/NTS in the modulation of the lipopolysaccharide/LPS induced dysfunction of the sympatho-adrenal-medullary system/SAM using both the NTS receptor 1/NTSR agonist PD149163/PD and antagonist SR48692 /SR. Forty eight mice were maintained in eight groups; Group I/control, Groups II, III, IV, and VII received LPS for 5 days further Group III/IV/VII received PD low dose/PD, PD high dose /PD and SR for 28 days respectively. Group V/VI received similar only PD and PD dose respectively whereas Group VIII was exposed to only SR for 28 days.
View Article and Find Full Text PDFJ Chem Ecol
January 2025
Institute of Zoology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
In modern agriculture, control of insect pests is achieved by using insecticides that can also have lethal and sublethal effects on beneficial non-target organisms. Here, we investigate acute toxicity and sublethal effects of four insecticides on the males' sex pheromone response and the female host finding ability of the Drosophila parasitoid Leptopilina heterotoma. The nicotinic acetylcholine receptor antagonists acetamiprid, flupyradifurone and sulfoxaflor, as well as the acetylcholinesterase inhibitor dimethoate were applied topically as acetone solutions.
View Article and Find Full Text PDFSci Rep
January 2025
Amrita School of Artificial Intelligences, Coimbatore, Amrita Vishwa Vidyapeetham, Coimbatore, India.
Lung cancer is the leading cause of cancer-related fatalities globally, accounting for the highest mortality rate among both men and women. Mutations in the epidermal growth factor receptor (EGFR) gene are frequently found in non-small cell lung cancer (NSCLC). Since curcumin and CB[2]UN support various medicinal applications in drug delivery and design, we investigated the effect of curcumin and CB[2]UN-based drugs in controlling EGFR-mutant NSCLC through a dodecagonal computational approach.
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