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:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Percutaneous transluminal coronary angioplasty (PTCA) is widely used to treat patients with ischemic heart disease, but the procedure involves a number of problems, including acute coronary occlusion and restenosis. Although stents have proved useful for preventing post-PTCA restenosis, especially elastic recoil during the acute phase, no method has yet been established to prevent restenosis caused by vascular smooth muscle cell proliferation in the late phase. Cilostazol selectively inhibits the 3'5'-cyclic-nucleotide phosphodiesterase (PDE) III (cyclic guanosine monophosphate-inhibited PDE) of the cyclic adenosine monophosphate PDE family; it also has antithrombotic and vasodilating effects, as well as an inhibitory effect on vascular smooth muscle cell proliferation through PDE III inhibition. From November 1995 to March 1997, the usefulness of cilostazol versus aspirin in preventing subacute thrombosis and restenosis was studied in 70 patients (55 men and 15 women; 82 total lesions) who had undergone successful elective Palmaz-Schatz stent implantation. Patients were randomly allocated to receive aspirin 81 mg/d (40 patients with 45 lesions) or cilostazol 200 mg/d (30 patients with 37 lesions) alone. There was no difference in patients or angiographic characteristics between these groups. No subacute thrombosis, acute complications (ie, death, emergent coronary artery bypass grafting, or hemorrhagic complications), or drug side effects were found in the cilostazol group. The minimal lumen diameter (mean +/- SD) at follow-up was 1.89 +/- 1.08 mm in the aspirin group (41 lesions, 5.63 +/- 1.74 months after stent implantation) and 2.34 +/- 0.74 mm in the cilostazol group (35 lesions, 5.14 +/- 1.91 months after stent implantation), revealing statistically significant dilatation in the cilostazol group. The restenosis rate was 26.8% in the aspirin group, compared with 8.6% in the cilostazol group; this difference was statistically significant. Administration of cilostazol alone after the implantation of intracoronary Palmaz-Schatz stents was useful for the prevention of subacute thrombosis and restenosis.
...
PMID:A randomized trial of aspirin versus cilostazol therapy after successful coronary stent implantation. 938 93

Cilostazol(6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4- dihydro-2(1H)-quinolinone) selectively inhibits cGMP-inhibited phosphodiesterase (PDE3) and is a potent inhibitor of platelet aggregation induced by various agonists. Effect of cilostazol on shear stress-induced human platelet aggregation (SIPA) was examined in vitro and ex vivo. Cilostazol inhibited SIPA dose-dependently in vitro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2.6 microM (m +/- SE, n=5), which was very similar to that (12.5 +/- 2.1 microM) for inhibition of ADP-induced platelet aggregation. Cilostazol potentiates the inhibition of SIPA by PGE1 and enhances its ability to increase cAMP concentrations. A single oral adminstration of 100 mg cilostazol to healthy volunteers produced a significant inhibition of SIPA. This study demonstrates that cilostazol is an effective inhibitor of SIPA, which may be important for the prevention and the treatment of arterial occlusive diseases.
...
PMID:Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo. 941 70

1. The effect of cilostazol, an inhibitor of phosphodiesterase type III (PDE III), on the contraction induced by histamine was studied by making simultaneous measurements of isometric force and the intracellular concentration of Ca2+ ([Ca2+]i) in endothelium-denuded muscle strips from the peripheral part of the middle cerebral artery of the rabbit. 2. High K+ (80 mM) produced a phasic, followed by a tonic increase in both [Ca2+]i and force. Cilostazol (10 microM) did not modify the resting [Ca2+]i, but it did significantly decrease the tonic contraction induced by high K+ without a corresponding change in the [Ca2+]i response. 3. Histamine (3 microM) produced a phasic, followed by a tonic increase in both [Ca2+]i and force. Cilostazol (3 and 10 microM) significantly reduced both the phasic and tonic increases in [Ca2+]i and force induced by histamine, in a concentration-dependent manner. 4. Rp-adenosine-3':5'-cyclic monophosphorothioate (Rp-cAMPS, 0.1 mM), a PDE-resistant inhibitor of protein kinase A (and as such a cyclic AMP antagonist), did not modify the increases in [Ca2+]i and force induced by histamine alone, but it did significantly decrease the cilostazol-induced inhibition of the histamine-induced responses. 5. In Ca2+-free solution containing 2 mM EGTA, both histamine (3 microM) and caffeine (10 mM) transiently increased [Ca2+]i and force. Cilostazol (1-10 microM) (i) significantly reduced the increases in [Ca2+]i and force induced by histamine, and (ii) significantly reduced the increase in force but not the increase in [Ca2+]i induced by caffeine. 6. In ryanodine-treated strips, which had functionally lost the histamine-sensitive Ca2+ storage sites, histamine (3 microM) slowly increased [Ca2+]i and force. Cilostazol (3 and 10 microM) lowered the resting [Ca2+]i, but did not modify the histamine-induced increase in [Ca2+]i, suggesting that functional Ca2+ storage sites are required for the cilostazol-induced inhibition of histamine-induced Ca2+ mobilization. 7. The [Ca2+]i-force relationship was obtained in ryanodine-treated strips by applying ascending concentrations of Ca2+ (0.16-2.6 mM) in Ca2+-free solution containing 100 mM K+. Histamine (3 microM) shifted the [Ca2+]i-force relationship to the left and increased the maximum Ca2+-induced force. Under the same conditions, whether in the presence or absence of 3 microM histamine, cilostazol (3-10 microM) shifted the [Ca2+]i-force relationship to the right without producing a change in the maximum Ca2+-induced force. 8. It is concluded that, in smooth muscle of the peripheral part of the rabbit middle cerebral artery, cilostazol attenuates the histamine-induced contraction both by inhibiting histamine-induced Ca2+ mobilization and by reducing the myofilament Ca2+ sensitivity. It is suggested that the increase in the cellular concentration of cyclic AMP that will follow the inhibition of PDE III may play an important role in the cilostazol-induced inhibition of the histamine-contraction.
...
PMID:Effect of cilostazol, a phosphodiesterase type III inhibitor, on histamine-induced increase in [Ca2+]i and force in middle cerebral artery of the rabbit. 953 15

Whether phosphodiesterase inhibitors increase the heart rate in patients with bradyarrhythmias is not known. We attempted to determine whether the oral phosphodiesterase inhibitor cilostazol exhibits beneficial chronotropic effects in patients with symptomatic bradyarrhythmias. Twenty patients comprising eight with bradycardic atrial fibrillation, eight with sick sinus syndrome, and four with Wenckebach-type atrioventricular block, whose 24-h total heart-beat count was < or =70,000 beats and whose maximal RR interval was > or =2.5 s, were enrolled. Holter recordings (24-h) were made before and 2 weeks after oral daily administration of 200 mg of cilostazol. Cilostazol increased the 24-h total heart-beat count from 77,429 +/- 11,168 to 107,981 +/- 13,536 (95% confidence interval, 24,605-36,497; p < 0.0001), the minimal heart rate from 33 +/- 9 47 +/- 13 beats/min (95% confidence interval, 9-19 beats/min; p < 0.0001), and the maximal RR interval from 3,149 +/- 1,018 to 2,087 +/- 601 ms (95% confidence interval, -1,517 to -608 ms; p = 0.0001). Only two patients had headaches as adverse effects. In conclusion, cilostazol had a beneficial positive chronotropic effect in patients with bradyarrhythmias, especially with bradycardic atrial fibrillation and sick sinus syndrome.
...
PMID:Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with bradyarrhythmias. 955 1

The effects of cilostazol, a selective cyclic AMP (cAMP) phosphodiesterase inhibitor, on retinal and choroidal blood flow and retinal arteriole diameter were examined in anesthetized rats. The retinal and choroidal blood flow was measured using laser Doppler flowmetry, and the diameter of the retinal arterioles was measured using digital video microscopy. Cilostazol was administered by two routes; systemically via the intravenous route, and directly into the retinal vessels via the intra-arterial route. When administered intravenously, 1 mg/kg of cilostazol produced a biphasic blood flow response, composed of an initial decrease which was dependent on a depressor response of mean arterial pressure, and a subsequent slight but significant increase which was independent of changes in mean arterial pressure. When administered intra-arterially over a 2-min period, 40-55 and 400-440 microg of cilostazol both produced an increase in the blood flow in a dose-dependent manner, while a depressor effect was observed only at the dose of 400-440 microg. The diameter of the retinal arterioles was increased after the intra-arterial injection of cilostazol (400 microg). It is concluded that intra-arterially administered cilostazol induces vasodilation of the retinal arterioles of rats, which results in an increase in blood supply to the retina, independent of changes in mean arterial pressure.
...
PMID:Cilostazol, a selective cAMP phosphodiesterase inhibitor, dilates retinal arterioles and increases retinal and choroidal blood flow in rats. 957 Apr 47

Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Our study was designed to investigate inhibitory effects of cilostazol on the expression of activation-dependent platelet membrane surface glycoproteins. We performed flow cytometric analysis using monoclonal antibodies, PAC-1 (antibody against activation dependent epitope of GPIIb/IIIa), anti-CD62P (P-selectin), and anti-CD63. In vitro ADP stimulation of platelets taken from seven healthy volunteers produced significant increases in the mean channel fluorescence intensities (MFI) for PAC-1 (148% increase) and CD62P (43% increase) but did not increase in that for CD63. The enhanced MFI for CD62P was suppressed to the control level by pretreatment with 1 microM (88% suppression), 3 microM (94% suppression), and 10 microM (95% suppression) of cilostazol. However, that of PAC-1 was suppressed to a lesser degree (12, 16, and 21% suppressions, respectively). Cilostazol may inhibit P-selectin release from alpha-granule, rather than activation-dependent conformational change of GPIIb/IIIa in platelets. Cilostazol inhibits cellular interaction among platelets, leukocytes, and vascular endothelial cells mediated by P-selectin.
...
PMID:Cilostazol inhibits the expression of activation-dependent membrane surface glycoprotein on the surface of platelets stimulated in vitro. 1003 Aug 30

Deficiencies in cellular cyclic AMP (cAMP) and nitric oxide (NO) production are thought to be involved in the pathogenesis of diabetic neuropathy. We used a human neuroblastoma cell line, SH-SY5Y, to investigate the effect of cilostazol, a specific cAMP phosphodiesterase inhibitor, on NO production and Na+, K+-ATPase activity. SH-SY5Y cells were cultured under 5 or 50 mM glucose for 5-6 days, the cells were then exposed to cilostazol or other chemicals and nitrite, cAMP and Na+, K+-ATPase activity were measured. In cells grown in 50 mM glucose, cilostazol was observed to increase significantly both NO production and cellular cAMP accumulation in a time- and dose-dependent manner. Cilostazol also significantly recovered reduced levels of protein kinase A activity (PKA) in 50 mM glucose. Furthermore, a PKA inhibitor, H-89 significantly suppressed the increase in NO production stimulated by cilostazol, suggesting that cilostazol stimulates NO production by activating PKA. Cilostazol did not affect either sorbitol or myo-inositol concentrations. Dexamethasone, which is known to induce inducible NO synthase, had no effect on NO production stimulated by cilostazol, suggesting that cilostazol stimulates NO production catalyzed by neuronal constitutive NO synthase (ncNOS) in SH-SY5Y cells. L-arginine, which is an NO agonist enhanced Na+, K+-ATPase activity in cells grown in 50 mM glucose, NG-nitro-L-arginine methyl ester (L-NAME), which is an NOS inhibitor inhibited basal Na+, K+-ATPase activity in 5 mM glucose and suppressed the increased enzyme activity induced by cilostazol in 50 mM glucose. The above results confirmed our previous observation that NO regulates Na+, K+-ATPase activity in SH-SY5Y cells and suggest that cilostazol increases Na+, K+-ATPase activity, at least in part, by stimulating NO production. The present results also suggest that cilostazol has a beneficial effect on diabetic neuropathy by improving Na+, K+-ATPase activity via directly increasing cAMP and NO production in nerves.
...
PMID:Cilostazol, a cyclic AMP phosphodiesterase inhibitor, stimulates nitric oxide production and sodium potassium adenosine triphosphatase activity in SH-SY5Y human neuroblastoma cells. 1050 60

Cilostazol is a potent cyclic nucleotide phosphodiesterase (PDE) type 3 (PDE3) inhibitor that was recently approved by the Food and Drug Administration (FDA) for the treatment of intermittent claudication. Its efficacy is presumed to be due to its vasodilatory and platelet activation inhibitory activities. Compared with those treated with placebo, patients treated with cilostazol showed a minimal increase in cardiac adverse events. Because of its PDE3 inhibitory activity, however, the possibility that cilostazol exerts positive cardiac inotropic effects is a safety concern. Therefore we compared the effects of cilostazol with those of milrinone, a selective PDE3 inhibitor, on intracellular cyclic adenosine monophosphate (cAMP) levels in platelets, cardiac ventricular myocytes, and coronary smooth muscle cells. We also compared the corresponding functional changes in these cells. Cilostazol and milrinone both caused a concentration-dependent increase in the cAMP level in rabbit and human platelets with similar potency. Furthermore, cilostazol and milrinone were equally effective in inhibiting human platelet aggregation with a median inhibitory concentration (IC50) of 0.9 and 2 microM, respectively. In rabbit ventricular myocytes, however, cilostazol elevated cAMP levels to a significantly lesser extent (p < 0.05 vs. milrinone). By using isolated rabbit hearts with a Langendorff preparation, we showed that milrinone is a very potent cardiotonic agent; it concentration-dependently increased left ventricular developed pressure (LVDP) and contractility. Cilostazol was less effective in increasing LVDP and contractility (p < 0.05 vs. milrinone), which is consistent with the cardiac cAMP levels. The cardiac effect of OPC-13015, a metabolite of cilostazol with about sevenfold higher PDE3 inhibition, was similar to cilostazol. Whereas milrinone concentration-dependently increased cAMP in rabbit coronary smooth muscle cells, cilostazol did not have such an effect. However, both compounds increased coronary flow equally in rabbit hearts. Our results show that although cilostazol and milrinone both inhibit PDE3, cilostazol preferentially acts on vascular elements (platelets and flow). This unique profile of cilostazol is consistent with its beneficial and safe clinical outcomes in patients with intermittent claudication.
...
PMID:Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells. 1051 Nov 23

Cilostazol, a novel potent inhibitor of phosphodiesterase, increases coronary flow. The effects of cilostazol on coronary flow velocity and coronary flow reserve were studied in 103 patients with coronary artery disease who underwent coronary angiography. Cilostazol 200 mg/day was administered for 3 months (31 patients) or 6 months (37 patients), and coronary flow reserve were measured before and after the cilostazol administration. Coronary flow reserve were measured twice at an interval of 6 months in the control group (35 patients). The Doppler guide wire was advanced into the coronary artery with no significant vessel stenosis. After obtaining continuous baseline coronary flow velocity, an intracoronary infusion of papaverine (10 mg) was performed to measure coronary flow reserve. There were no significant differences in coronary flow velocity just before intracoronary papaverine infusion between the initial and follow-up studies in any of the 3 groups. Coronary flow reserve increased significantly after cilostazol administration in the 3 months and 6 months groups compared with before administration (3 months group: 2.8 +/- 0.8 vs 2.4 +/- 0.9, p < 0.05; 6 months group: 2.8 +/- 1.0 vs 2.4 +/- 0.7, p < 0.01). However, there was no significant difference in coronary flow reserve in the control group between follow-up and initial studies (2.7 +/- 0.8 vs 2.5 +/- 0.8, NS). In conclusion, the long-term oral administration of cilostazol for 3 or 6 months improves coronary flow reserve.
...
PMID:[Effect of long-term cilostazol administration on coronary flow velocity and coronary flow reserve]. 1055 34

An 86-year-old man had a history of hypertension and had been treated with calcium antagonist but no medications that could reduce heart rate. As a 12-lead electrocardiogram showed sinus bradycardia, complete right bundle branch block and left anterior fascicular hemiblock on his first visit to our hospital on January 1998, he was admitted to our hospital for further examination and treatment. A 24-hour Holter electrocardiogram demonstrated a total number of 74,182 heartbeats per day with pauses (> 2.0 sec) of 187/day. Overdrive atrial pacing study and His bundle electrogram revealed a prolonged corrected sinus node recovery time (5.820msec at a stimulation rate of 130/min) and H-V conduction time (80msec) with normal A-H conduction time, respectively. We diagnosed these abnormalities as sick sinus syndrome (Rubenstein II). His activity of daily living score was 30 points by the Barthel index on the day of admission. Oral administration of orciprenaline sulfate (30 mg/day), a beta-adrenoceptor agonist, was initially chosen rather than implantation of a cardiac pacemaker to increase his heart rate since he did not have any symptoms due to bradycardia and he did not give us an informed consent for the implantation. Orciprenaline sulfate, however, failed to increase total heartbeats (73,079/day). Then, oral cilostazol (100 mg/day), a phosphodiesterase III inhibitor, was administered. After two weeks of the regimen total heart beats were increased (85,642/day) with no pauses. The increase in heart rate resulted in the improvement of his activity of daily living (Barthel index: 55 points). Cilostazol could be the first line medication for elderly patients with bradyarrhythmia in whom implantation of cardiac pacemaker is not absolutely indicated.
...
PMID:[Cilostazol increased heart rate with improvement of activity of daily living in an elderly patient with sick sinus syndrome]. 1055 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---