Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.2 (
guanylate cyclase
)
8,497
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Monoamine oxidase (MAO) catalyzes the biological degradation of the neurotransmitters monoamines. The altered substrate specificity of MAO may be of pathogenic importance in some cases and MAO inhibitors showed a therapeutical effect in the experimental setting. Analyzing the efficacy of various compounds in inhibiting
MAO A
and B revealed new approaches to designing new-generation MAO inhibitors. Tribulin is a fraction of endogenous MAO inhibitors that are present in human and animal tissues and biological fluids. Isatin is an endogenous indole which was initially derived from a tribulin fraction. An investigation of the biological properties of tribulin revealed its heterogeneity and some chemical components were identified. It was shown that deficiency of tribulin components that selectively inhibited
MAO A
long with a larger number of molecules of this enzyme might be of great importance for the development of alcoholism. In addition to MAO inhibition, the physiological concentrations of isatin inhibited the receptor-binding of atrial natriuretic peptides and ANP-stimulated
guanylate cyclase
(GC). The sensitivity of ANP-GC to isatin might be allosterically regulated. Selective antagonists of natriuretic peptide receptors were found among isatin analogues which may be an effective pharmacological tool for further studies of the role of natriuretic peptides in the body.
...
PMID:[Monoamine oxidase, tribulin, isatin: basic and applied medical aspects]. 1057 64
Several activators of soluble
guanylate cyclase
were investigated as potential inhibitors of rat liver mitochondrial monoamine oxidases (MAO) A and B. They all fitted into the previously designed "molds" of substrate-inhibitor binding sites of these enzymes. However, only two of them, NO donors (7-nitro-benzotetrazine-1,3-dioxide (7-NBTDO) and benzodifuroxan), caused nonselective inhibition of
MAO A
and MAO B with IC(50) values of 1.3-1.6 and 6.8-6.3 microM, respectively. The inhibitory effect on both
MAO A
and MAO B was reduced by mitochondria wash suggesting reversible mode of the enzyme inhibition. There was no correlation between potency of MAO inhibition and activation of human platelet soluble
guanylate cyclase
. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) had no effect on the manifestation of MAO inhibition by benzodifuroxan and 7-NBTDO; however, at 50 microM concentration carboxy-PTIO caused potent inhibition of
MAO A
with minor effect on MAO B activity. The data suggest that nonselective inhibition of
MAO A
and MAO B by benzodifuroxan and 7-NBTDO can be attributed to the properties of the chemical structures of these compounds. The results of the present study demonstrate a real possibility for the development of a new generation of effective reversible nonselective MAO inhibitors exhibiting equal inhibitory activity with respect to both
MAO A
and MAO B.
...
PMID:Nonselective inhibition of monoamine oxidases A and B by activators of soluble guanylate cyclase. 1460 50
