Soluble guanylyl cyclase (sGC) is the principal enzyme in mediating the biological actions of nitric oxide. On activation, sGC converts guanosine triphosphate to guanosine 3',5'-cyclic monophosphate (cGMP), which mediates diverse physiological processes including vasodilation, platelet aggregation, and myocardial functions predominantly by acting on cGMP-dependent protein kinases[1].Impaired NO-sGC-cGMP signaling could lead to osteoblast apoptosis by mechanisms involving the oxidative-stress-induced shift of the redox state of the reduced heme to oxidized sGC, leading to diminished heme binding to the enzyme and rendering the sGC unresponsive to NO. Targeting oxidized sGC to enhance cGMP production could restore proliferation and differentiation of osteoblasts into osteocytes[2]. ODQ is a potent and selective sGC inhibitor. ODQ enhances the pro-apoptotic effects of Cisplatin in human mesothelioma cells. At 30 and 50 μM, ODQ causes significant induction of apoptosis in the NCI-H2452 cells, elevating apoptotic levels by 12 fold and 15 fold, respectively. At 10μM, a concentration below the threshold for induction of apoptosis by ODQ, ODQ in combination with Cisplatin enhanced (in fact, doubled) the pro-apoptotic effects of Cisplatin at 1 μM[3]. ODQ (2 mg/kg; i.p.) reduces the multiple organ injury and dysfunction caused by wall fragments of Gram-positive or Gram-negative bacteria in the anesthetized rat[4].
ODQ 细胞实验
Cell Line
Concentration
Treated Time
Description
References
DU-145 cells
50 µM
48 hours
ODQ activated caspase-3 at 50 μM, promoting apoptosis.
Br J Pharmacol. 2008 Nov;155(6):804-13
PC-3 cells
50 µM
48 hours
ODQ activated caspase-3 at 50 μM, promoting apoptosis.
Br J Pharmacol. 2008 Nov;155(6):804-13
Human platelets
10 µM
10 min
ODQ inhibited VASP phosphorylation, but after prolonged incubation (3 min or longer) with NO donor, VASP phosphorylation signals recovered.
Br J Pharmacol. 2013 Sep;170(2):317-27
Murine platelets
10 µM
10 min
ODQ reduced NO-induced cGMP increases, but at high NO donor concentrations (100 μM DEA-NO), ODQ lost its inhibitory effect.
Br J Pharmacol. 2013 Sep;170(2):317-27
HEK-GC cells
1, 10, 100 µM
10 min
ODQ reduced NO-induced cGMP increases, but even at a concentration of 100 μM ODQ the NO-induced cGMP production was not completely abrogated.
Br J Pharmacol. 2013 Sep;170(2):317-27
Cytosolic extracts from aortic rings and cardiomyocytes
50 µM
10 minutes
To investigate the effects of ODQ on SNAP-induced increases in cGMP levels. In cytosolic extracts, ODQ reduced these effects by about 50%.
Br J Pharmacol. 1999 Jun;127(3):693-700
Rat ventricular cardiomyocytes
50 µM
10 minutes
To investigate the effects of ODQ on SNAP-, DETA NONOate-, and carbachol-induced increases in cGMP levels. In cardiomyocytes, ODQ did not affect these effects.
Br J Pharmacol. 1999 Jun;127(3):693-700
Rat aortic rings
50 µM
10 minutes
To investigate the effects of ODQ on SNAP-, DETA NONOate-, and carbachol-induced increases in cGMP levels. In aortic rings, ODQ completely abolished these effects.
Br J Pharmacol. 1999 Jun;127(3):693-700
Rat coronary arteries
5 µM
20 minutes
To investigate the effect of ODQ on dapagliflozin-induced vasodilation, results showed that ODQ did not affect dapagliflozin-induced vasodilation.
Int J Mol Sci. 2023 Nov 28;24(23):16873
HEK293 cells
10 µM
30 minutes
Measure intracellular cGMP levels, ODQ inhibited the effects of VL-102 and YC-1.
Cephalalgia. 2018 Jul;38(8):1471-1484
Normal human prostate epithelial cells (HPrECs)
10 µM
48 hours
ODQ at 10 μM did not activate caspase-3, indicating no apoptotic effect on normal cells.
Br J Pharmacol. 2008 Nov;155(6):804-13
LNCaP cells
0.1 µM to 100 µM
48 hours
ODQ activated caspase-3 at 50 and 100 μM, promoting apoptosis, and caused DNA fragmentation and nucleosome accumulation at 100 μM.
Br J Pharmacol. 2008 Nov;155(6):804-13
ODQ 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL6/J mice
Chronic nitroglycerin migraine model
Intraperitoneal injection
1 mg/kg
Every other day for 9 days
ODQ completely blocked acute and chronic hyperalgesia induced by nitroglycerin.
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