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:2.7.11.12 (
PKG
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Extracellular diadenosine polyphosphates (Ap
n
A) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular Ap
n
A cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie Ap
n
A action in the heart remain unknown. In the present study the role of the P2Y-associated intracellular regulatory pathway in the mediation of diadenosine
tetraphosphate
(Ap
4
A) effects in the rat heart has been investigated for the first time. Extracellular Ap
4
A caused significant decreasing of the ventricular inotropy. Ap
4
A evoked reduction of the left ventricle contractility in the isolated Langendorff-perfused rat hearts, decreasing of the Ca
2+
transients in the enzymatically isolated ventricular cardiomyocytes and induced shortening of action potentials in the ventricle multicellular preparations. The inhibitory effects of Ap
4
A in the rat heart were significantly attenuated by protein kinase C (PKC) inhibitor chelerythrine but these effects were not affected by NO-synthase inhibitor L-NAME and guanylyl cyclase (sGC) inhibitor ODQ. In addition, substantial attenuation of Ap
4
A-caused negative inotropy in the left ventricle was produced by nonselective phsophodiesterase (PDE) inhibitor IBMX, while PDE type 2 inhibitor EHNA was ineffective. In conclusion, our results allow suggesting that Ap
4
A-induced inhibitory effects in the rat heart are mediated by PKC, but not by NO/sGC/
PKG
-related signaling pathway. In addition, PDE stimulation may contribute to Ap
4
A-caused inhibition of the rat heart contractility.
...
PMID:Negative inotropic effects of diadenosine tetraphosphate are mediated by protein kinase C and phosphodiesterases stimulation in the rat heart. 2923 60
