In this study we determined the effect of cholinoceptor agonist pilocarpine on the stimulation of nitric oxide synthase (NOS) and on prostaglandin E2 (PGE2) generation upon rat dental pulp. By reverse transcriptase/polymerase chain reaction (RT-PCR) we identified several products corresponding to m1, m2, m3, and m4 muscarinic acetylcholine receptors (mAChRs). The stimulation of M1, M2, M3, and M4 mAChRs by pilocarpine increases NOS activity and PGE2 generation. There is a correlation (correlation coefficient=0.05) between NOS activity and PGE2 generation through the activation of phosphoinositide by phospholipase C (PLC), phospholipase A2 (PLA2), and cyclooxygenase 1 (COX-1). Exogenous PGE2 restored NOS activity inhibited by indomenthacin (INDO), whereas nitric oxide (NO) donor restored PGE2 generation inhibited by NG-methyl-L-arginine acetate salt (L-NMMA). These data indicate that both NO and PGE2 interact with their own respective biosynthetic pathways modulating NOS and COX activities. Results could contribute to understanding the involvement of NO and PGE2 in healthy dental pulp given that cellular signals through the parasympathetic system modulate the function of the dentin-pulp complex.
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http://dx.doi.org/10.1016/j.joen.2006.11.009 | DOI Listing |
Alzheimers Dement
December 2024
University of Southern California, Los Angeles, CA, USA.
Background: Synaptic loss predicts cognitive decline in Alzheimer's disease (AD). However, the critical disease modifying molecular mechanisms of synaptic failure remain elusive. Animal studies implicate the increased activation of cytosolic phospholipase (cPLA2) activation in synaptic loss and neuroinflammation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Background: Multiple AD risk genes are implicated in lipid metabolism, and plasma and brain lipid levels are altered in AD. Astrocytes are enriched in key lipid-related factors and are likely contributors to altered lipid homeostasis in AD. We hypothesize that APP/Aβ-related pathology and neuroimmune factors modulate astrocytic gene transcription that promote maladaptive changes in lipid pathways, including aberrant astrocytic production and release of lipids that could affect Aβ pathology and neuronal deficits.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address:
The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide pyrazole moieties 4, 5, 6a-e, and 7a-f with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC values ranging between 0.05 and 0.
View Article and Find Full Text PDFNeurochem Int
December 2024
Master and PhD Programs in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, 970, Taiwan; Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, 970, Taiwan. Electronic address:
Previous studies have shown that celecoxib or NSAID may paradoxically induce cyclooxygenase-2 (COX-2) expression and trigger inflammation-like responses in airway smooth muscle cells and renal mesangial cells. Despite the extensive research on celecoxib, its atypical biological effect on the induction of COX-2 in astroglial cells within the central nervous system (CNS) remains unexplored. In the present study, we investigated the impact of celecoxib on COX-2 and Glial Fibrillary Acidic Protein (GFAP) expression and explored the mechanisms underlying celecoxib-regulated COX-2 expression in cortical astrocytes of rats.
View Article and Find Full Text PDFFront Neurosci
December 2024
Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Background: Seizures can cause as well as result from neuroinflammation. This study was performed to identify the hematologic inflammatory parameters (HIPs) and inflammatory mediators that change after a single seizure in a canine pentylenetetrazole (PTZ)-induced seizure model.
Methods: Five healthy Beagle dogs were used in this study.
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