Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3':5'-Cyclic-AMP phosphodiesterase (EC 3.1.4.17) and the activating factor of cyclic nucleotide phosphodiesterase were detected in cultured human cell lines from patients with lymphoblastic leukemia and retinoblastoma and in the Brown-Pearce (rabbit) carcinoma. The homogenate of lymphoblasts contained levels of the activating factor in excess of that required to produce maximal activation of the endogenous phosphodiesterase. The activating factor found in these malignant cells appears to be similar to the calcium-binding protein activator of bovine brain phosphodiesterase on the basis of the molecular weight obtained from gel filtration, electrophoretic patterns, calcium requirement for the activity, and the effect of calcium on the proteolysis. In addition, the tumor-derived activator was able to restore the activity of activator-deficient phosphodiesterase from the bovine brain.
 ...
PMID:Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma. 20 Jul 56

Transplantable Brown-Pearce carcinoma was adapted successfully in the rabbit anterior chamber. Regression of tumor growth was attained on tri-weekly perfusion of the AC with 10 micromolar of methotrexate. Tumor cyclic nucleotide phosphodiesterase (PDE) and protein activator were found to be markedly depressed during the course of chemotherapy and the PDE cAMP/cGMP ratio was similarly altered. Corroborative light and electron-microscopic studies showed specific alterations of intracellular organelles in relation to MTX and tumor cell death. These findings suggest that metabolic pathways of cyclic nucleotides are important biochemical modulators of neoplastic cells. The method of intraocular perfusion precludes systemic toxic effects and avoids compromising the animals' immunocompetence.
 ...
PMID:Experimental intraocular malignancy: the effect of intracameral perfusion. 23 85

A novel series of benzodiazepine derivatives have been discovered as inhibitors of PDE4 enzymes. We have found that our compounds are selective versus other PDE enzymes, and that the activity can be modulated by specific structural modifications. One compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized Brown-Norway rats (compound 9, 5.1 mg/kg p.o.), moreover this compound is not emetic at 3 mg/kg i.v.
 ...
PMID:Synthesis and structure-activity relationships of 4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indoles: novel PDE4 inhibitors. 1063 38

Vasopressin-stimulated insertion of the aquaporin 2 (AQP2) water channel into the plasma membrane of kidney collecting duct principal cells is a key event in the urinary concentrating mechanism. The paradigm for vasopressin-receptor signaling involves cAMP-mediated protein kinase A activation, which results in the functionally critical phosphorylation of AQP2 on amino acid serine 256. We previously showed that a parallel cGMP-mediated signaling pathway also leads to AQP2 membrane insertion in AQP2-transfected LLC-PK1 (LLC-AQP2) cells and in outer medullary collecting duct principal cells in situ (Bouley R, Breton S, Sun T, McLaughlin M, Nsumu NN, Lin HY, Ausiello DA, and Brown D. J Clin Invest 106: 1115-1126, 2000). In the present report, we show by immunofluorescence microscopy, and Western blotting of plasma membrane fractions, that 45-min exposure of LLC-AQP2 cells to the cGMP phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate (Viagra) or 4-{[3',4'-methylene-dioxybenzyl]amino}-6-methoxyquinazoline elevates intracellular cGMP levels and results in the plasma membrane accumulation of AQP2; i.e., they mimic the vasopressin effect. Importantly, our data also show that acute exposure to PDE5 inhibitors for 60 min induces apical accumulation of AQP2 in kidney medullary collecting duct principal cells both in tissue slices incubated in vitro as well as in vivo after intravenous injection of Viagra into rats. These data suggest that AQP2 membrane insertion can be induced independently of vasopressin-receptor activation by activating a parallel cGMP-mediated signal transduction pathway with cGMP PDE inhibitors. These results provide proof-of-principle that pharmacological activation of vasopressin-independent, cGMP signaling pathways could aid in the treatment of those forms of nephrogenic diabetes insipidus that are due to vasopressin-2 receptor dysfunction.
 ...
PMID:Stimulation of AQP2 membrane insertion in renal epithelial cells in vitro and in vivo by the cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra). 1564 88

Physiological aging is a significant risk factor in the on-set of male erectile dysfunction (ED) and an imbalance in factors that modulate cavernosal smooth-muscle tone may play a role in these altered penile hemodynamic mechanisms. To evaluate the association between aging and male erectile function, we monitored neurogenic erectile response and its correlation to systemic arterial pressure changes in old (21-23 months of age) vs young (6-9 months of age) Brown-Norway (BN) rats. We tested the hypothesis that age-associated ED is due to unregulated vasoconstrictive tone, contributed in part by an increased Rho-kinase activity, and that antagonism of Rho-kinase activity attenuates the age-related decline in male erectile function. We also examined the hypothesis that a combination of Rho-kinase antagonism and phosphodiesterase-5 (PDE-5) inhibition has a synergistic effect in improving the erectile response in these aging animals. Erectile function in old BN rats was evaluated before and after intracavernosal injection of a specific inhibitor of Rho-kinase (Y-27632) alone or in combination with zaprinast, a PDE-5 inhibitor. Erectile capabilities of the young and old BN rat groups were significantly different in corpus cavernosum pressure response after electrical-field stimulation of the major pelvic ganglion. Y-27632 administration attenuated the aging-related changes in male erectile function seen in BN rats. Rho-kinase antagonism and PDE-5 inhibition had a synergistic effect in improving erectile function in old rats. Our data indicate that aging leads to impairment in the neurogenic erectile response in BN rats involving a possible derangement in penile hemodynamic mechanisms of the erectile tissue. Rho-kinase inhibition may be of value in treating age-related ED.
 ...
PMID:Rho-kinase inhibition improves erectile function in aging male Brown-Norway rats. 1571 24