Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release and synthesis in response to drugs that raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. Anterior pituitaries from ovariectomized rats were incubated with or without drugs in the presence of GnRH and [3H]glucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) (10 mM), cholera toxin (10 micrograms/ml), nor phosphodiesterase inhibitors [theophylline, 2 and 8 mM; 3-isobutyl-1-methylxanthine (MIX), 0.2 mM] had any detectable effect on release of immunoreactive LH (IR-LH) when used alone. However, 8-Br-cAMP and the inhibitors potentiated (P less than 0.01) GnRH-induced release of IR-LH. Total radiolabeled LH in the system was elevated (P less than 0.01) by either GnRH, 8-Br-cAMP for cholera toxin, but reduced (P less than 0.01) by 8 mM theophylline and unaffected by MIX or 2 mM theophylline. 8-Br-cAMP did not alter the effect of GnRH on radiolabeled LH in the total system, whereas MIX and 2 mM theophylline reduced (P less than 0.05) it. These results suggest that 1) cAMP does not effect LH release directly, but may interact with GnRH to potentiate it, 2) GnRH and cAMP have a similar mode of action on LH glycosylation, and 3) phosphodiesterase inhibitors have additional actions that interfere with LH glycosylation.
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PMID:Effects of GnRH and drugs that affect cAMP levels on LH synthesis and release. 616 3

The aim of this study was to investigate the influence of substances that increase intracellular cAMP levels on the aqueous humor outflow facility (C) of isolated bovine anterior segments. Anterior segments were perfused in vitro at a constant pressure of 10 mmHg for 270 min with a general protocol as follows: 90 min control perfusion with DMEM, 90 min of experimental perfusion with DMEM containing the test drug(s), and 90 min of postdrug-perfusion with DMEM. C was calculated as the ratio between the rate of medium inflow (microliter/min) and the perfusion pressure (mmHg). Anterior segments can be perfused in vitro for up to 5 hr without significantly modifying their C. The addition of epinephrine, forskolin, dibutyryl-cAMP or isobutylmethylxanthine to the control perfusion medium elicited a significant increase of C. If, during isobutylmethylxanthine perfusion, forskolin or epinephrine was added, C increased significantly. Finally, perfusion with indomethacin prior to addition of epinephrine prevented the increase of C induced by epinephrine. Epinephrine, the adenylate cyclase activator forskolin, the cAMP analog dibutyryl-cAMP, and the phosphodiesterase inhibitor isobutylmethylxanthine all increase aqueous facility. It seems reasonable to suspect that the cAMP system is involved in epinephrine's effects on bovine trabecular meshwork cells. Moreover, the complete inhibition by indomethacin of the outflow facility increase induced by epinephrine suggests that prostaglandins may be involved in the outflow facility mechanisms related to adrenoreceptor stimulation of trabecular meshwork cells.
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PMID:Facility changes mediated by cAMP in the bovine anterior segment in vitro. 906 27

Sildenafil is one of the most commonly used drugs for sexual dysfunction or to increase libido, and it regulates endothelial nitric oxide synthase enzyme via selective phosphodiesterase-V inhibition. Sildenafil can be easily obtained without a medical indication or prescription yet it is not considered as a completely safe medication. Hemoptysis and hemorrhagic stroke are some important adverse effects of sildenafil. The case of the current report was a 67-year-old diabetic patient with simultaneous anterior and posterior segment hemorrhage after the use of 100 mg sildenafil citrate. Anterior chamber clearance and pars plana vitrectomy were performed for the patient because the hyphema and vitreous hemorrhage did not resolve during the follow-up period. There are very limited data available in the literature suggesting an increase in the risk of hyphema or vitreous hemorrhage due to the use of sildenafil. This is the first report that reveals the bleeding effect of sildenafil use in a patient with type 2 diabetes.
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PMID:Intraocular Hemorrhage due to use of Sildenafil in a Patient with Diabetes. 3038 1