PMID: 9194695Jan 1, 1997Paper

Mechanism of the inhibition of neuronal nitric oxide synthase by 1-(2-trifluoromethylphenyl) imidazole (TRIM)

Life Sciences
R L Handy, P K Moore

Abstract

We have previously reported that 1-(2-trifluoromethylphenyl) imidazole (TRIM) is a potent inhibitor of mouse cerebellar neuronal NOS (nNOS) in vitro with very much reduced activity against bovine aortic endothelial NOS (eNOS). Using purified rat brain nNOS as enzyme source we have now probed the mechanism of action of TRIM. nNOS activity was linear over the first 5 min incubation. Optimal enzyme activity occurred in the presence of NADPH (0.5 mM), calcium chloride (75 microM), tetrahydrobiopterin (12 microM) and calmodulin (10 microg/ml) as cofactors. TRIM was a poor inhibitor of nNOS (IC50, 462.0 microM) compared with L-N(G) nitro arginine (L-NOARG, IC50, 0.32 microM). Removal of tetrahydrobiopterin (but not calmodulin) from the incubation medium greatly enhanced the nNOS inhibitory activity of TRIM (IC50, 32.0 microM) but not L-NOARG (IC50, 0.34 microM). In the absence of added tetrahydrobiopterin, TRIM competed with L-arginine for the substrate binding site on the nNOS enzyme with a Ki value of 47.3 microM. The present experiments suggest that TRIM interferes with the binding of both L-arginine and tetrahydrobiopterin to their respective sites on the nNOS enzyme.

References

Nov 30, 1992·Biochemical and Biophysical Research Communications·N E Rogers, L J Ignarro
Mar 1, 1994·The Biochemical Journal·R G Knowles, S Moncada
Aug 30, 1994·Biochemical and Biophysical Research Communications·C K Mittal, A L Jadhav
Feb 1, 1995·Trends in Biotechnology·J E Ogden, P K Moore
Jan 1, 1995·Annual Review of Physiology·J Garthwaite, C L Boulton

❮ Previous
Next ❯

Citations

Nov 10, 1998·Journal of the Autonomic Nervous System·C E SearsD J Paterson
Apr 3, 1999·Journal of the Autonomic Nervous System·K Conlon, C Kidd
Dec 4, 2001·Brain Research. Molecular Brain Research·M Fernández-CancioJ J Centelles
Jun 14, 2006·Nitric Oxide : Biology and Chemistry·Yan CheChun Guang Li
Feb 17, 2001·Nitric Oxide : Biology and Chemistry·V SorrentiA Vanella
Jan 20, 2010·Pharmaceuticals·Gregers Wegener, Vallo Volke
Aug 5, 1999·The Journal of Physiology·T J Koh, J G Tidball
Jul 12, 2002·Medicinal Research Reviews·Christos A Kontogiorgis, Dimitra Hadjipavlou-Litina
Nov 13, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Tadeusz J ScisloDonal S O'Leary
Feb 20, 2014·Chemical Society Reviews·Paramita MukherjeeRichard B Silverman
May 16, 2017·Frontiers in Physiology·Thássio R R MesquitaSandra Lauton-Santos
Nov 16, 2001·American Journal of Physiology. Heart and Circulatory Physiology·J K ChoateD J Paterson
Apr 24, 2003·Experimental Biology and Medicine·C Di GiacomoA Vanella
Oct 28, 2008·American Journal of Physiology. Heart and Circulatory Physiology·L S A CapettiniV S Lemos

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.