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:3.5.1.4 (
deaminase
)
5,113
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Activation of mineralocorticoid receptor antagonists (MRAs) is cardioprotective; however, this property is lost upon blockade or inactivation of adenosine (ADO) receptor A
2b
. In this study, we investigated whether the effects of MRAs are mediated by an interaction between cardioprotective ADO receptors A
1
and A
3
. Spironolactone (SPI) or eplerenone (EPL) increased ADO levels in the plasma of treated animals compared to control animals. SPI or EPL increased the protein and activity levels of ecto-5'-nucleotidase (
NT5E
), an enzyme that synthesizes ADO, compared to control. The levels of ADO
deaminase
(ADA), which degrades ADO, were not affected by SPI or EPL; however, the activity of ADA was reduced in SPI-treated rats compared to control. Using an isolated cardiomyocyte model, we found inotropic and chronotropic effects, and increased calcium transient [Ca
2+
]
i
in cells treated with ADO receptor A
1
or A
3
antagonists compared to control groups. Upon co-treatment with MRAs, EPL and SPI fully and partially reverted the effects of receptor A
1
or A
3
antagonism, respectively. Collectively, MRAs in vivo lead to increased ADO bioavailability. In vitro, the rapid effects of SPI and EPL are mediated by an interaction between ADO receptors A
1
and A
3
.
...
PMID:Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters. 3182 90
