Search results for "Purinones"
showing 5 items of 5 documents
Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina.
2013
nherited retinal degenerations affecting both rod and cone photoreceptors constitute one of the causes 74 of incurable blindness in the developed world. Cyclic guanosine monophosphate (cGMP) is crucial in the 75 phototransduction and, mutations in genes related to its metabolism are responsible for different retinal 76 dystrophies. cGMP-degrading phosphodiesterase 6 (PDE6) mutations cause around 4e5% of the retinitis 77 pigmentosa, a rare form of retinal degeneration. The aim of this study was to evaluate whether phar- 78 macological PDE6 inhibition induced retinal degeneration in cone-enriched cultures of porcine retina 79 similar to that found in murine models. PDE6 inhibition was induced…
Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels
2000
Abstract Background . Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. Methods . Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was…
A high-throughput chemical screen in DJ-1β mutant flies identifies zaprinast as a potential Parkinson's disease treatment
2021
AbstractDopamine replacement represents the standard therapy for Parkinson’s disease (PD), a common, chronic, and incurable neurological disorder; however, this approach only treats the symptoms of this devastating disease. In the search for novel disease-modifying therapies that target other relevant molecular and cellular mechanisms, Drosophila has emerged as a valuable tool to study neurodegenerative diseases due to the presence of a complex central nervous system, the blood–brain barrier, and a similar neurotransmitter profile to humans. Human PD-related genes also display conservation in flies; DJ-1β is the fly ortholog of DJ-1, a gene for which mutations prompt early-onset recessive P…
Sildenafil protects epithelial cell through the inhibition of xanthine oxidase and the impairment of ROS production
2009
Recent reports suggest that xanthine oxidase (XO), a modified form of the native xanthine dehydrogenase enzyme, plays an important role in various forms of ischemic and vascular injuries, inflammatory diseases, and chronic heart failure. The XO inhibitors allopurinol and its oxidation product oxypurinol held considerable promises in the treatment of these conditions both in experimental animals and in human clinical trials. More recently, an endothelium-based protective effect of sildenafil, a well-known type-5 phosphodiesterase inhibitor, has been reported in preconditioning prior to ischemia/reperfusion in healthy human subjects. Based on the structural similarities between allopurinol an…
Role of cyclic nucleotide phosphodiesterase isoenzymes in contractile responses of denuded rat aorta related to various Ca 2+ sources
2001
We have examined the cyclic nucleotide phosphodiesterase isoforms (PDE) involved in the contractile response of rat aorta to different agonists and different experimental procedures for use in functional studies. The inhibitory effect of AAL 05 on the different PDEs isolated from bovine aortic smooth muscle was examined. Compound AAL 05 appeared to be a selective PDE3 inhibitor. We analyzed the ability of the non-selective inhibitor IBMX (3-isobutyl-1-methylxanthine) and the isoenzyme selective inhibitors nimodipine (type 1), AAL 05 (6-(N-methyl-N-cyclohexyl butyl carboxamide) quinolin-2-one) and SKF 94120 (5-(4-acetamidophenyl) pyrazin-2(1H)-one; type3), rolipram (type4) and zaprinast (typ…