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

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

Some potent phosphodiesterase (PDE)-inhibiting dipyridamole derivatives are able to increase the primary immune response in mice immunized with sheep red blood cells (SRBC). 10mg/kg/day of the most potent substance administered in the drinking water increased the number of plaque forming cells (PFC) in spleens of these mice by a factor of about 2 when the treatment was started after immunization. Pretreating the animals did not result in an enhancement of numbers of plaque forming cells. There was no increase in the background number of PFC.
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PMID:Enhancement of the immune response to sheep erythrocytes in mice by phosphodiesterase-inhibiting dipyridamole derivatives. 608 39

Pure frog retina rod outer segments (ROS) preparations (A280/A500 = 2,1-2,3) catalyze the synthesis of ATP from ADP in the presence of Mg2+. Adenylate kinase (AK) (ATP:AMP phosphotransferase, EC 2.7.4.3) specific activities for ROS preparations are within the range 2-4 mumole per hour for mg protein. The enzymatic activity of investigated preparations is due to intact, but not destroyed ROS. The component which possesses AK is found in water-soluble, but not in membranous ROS fractions and seems to be a part of the predominant ROS plasma protein--GTP-binding complex of transducin. It has been shown, that this component is the T beta subunit of transducin and its enzymatic activity is controlled by other subunits of the transducin complex. The obtained results indicate that GDP kinase (ATP:GDP phosphotransferase, EC 2.7.4.6) activity of transducin depends on the work of both of T beta and T alpha subunits. It has been shown that in the ROS preparations synthesis of the ATP from ADP and GDP phosphorylation are stimulated by a lowering of Ca2+ concentration (less than 10(-5)-10(-7) M). T beta component is suggested to play the role of phosphotransferase which phosphorylates GDP associated with the T alpha subunits and it leads to formation of a complex T alpha X GTP which is an activator of vertebrate retina ROS phosphodiesterase.
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PMID:[Adenylate kinase and GDP-kinase activity of rod outer segments in the frog retina. Possible functional role of the T beta subunit of transducin]. 608 68

An early event associated with the stimulation of various secretory cells is the breakdown of phosphatidylinositol 4,5-bisphosphate and the mobilization of cellular calcium. Hydrolysis of this inositol lipid by a phosphodiesterase produces inositol trisphosphate (InsP3), a small water-soluble molecule which may serve a messenger function to release Ca2+ from internal stores. In order to assess the role of inositol lipid breakdown in the stimulation of insulin secretion we have examined the effect of InsP3 on Ca2+ fluxes in three different insulin-secreting tumor cells permeabilized by the addition of saponin. A rapid, transient release of Ca2+ from a non-mitochondrial pool occurred upon addition of InsP3 to all three cell types. Half-maximal Ca2+ release from the RIN-1046-38 and RIN-m5F cells was obtained in the concentration range 0.1-0.2 microM. However, the cells obtained from a transplantable tumor of the Syrian hamster were far more sensitive to InsP3 with half-maximal release being observed at 0.025 microM. A partially purified preparation of vesicles was isolated from this tumor which retained its responsiveness to InsP3. Half-maximal Ca2+ release from the vesicles was obtained at 0.2 microM InsP3. Our data are consistent with a role for InsP3 in mediating the increase in cytosolic free Ca2+ which occurs in response to a number of stimuli that promote the secretion of insulin.
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PMID:The effect of inositol trisphosphate on Ca2+ fluxes in insulin-secreting tumor cells. 609 55

(Sp)-2'-Deoxyadenosine 5'-O-[1-17O,1-18O,1,2-18O]triphosphate has been synthesized by desulfurization of (Sp)-2'-deoxyadenosine 5'-O-(1-thio[1,1-18O2]diphosphate) with N-bromosuccinimide in [17O]water, followed by phosphorylation with phosphoenolpyruvate-pyruvate kinase. A careful characterization of the product using high-resolution 31P NMR revealed that the desulfurization reaction proceeded with approximately 88% direct in-line attack at the alpha-phosphorus and 12% participation by the beta-phosphate to form a cyclic alpha,beta-diphosphate. The latter intermediate underwent hydrolysis by a predominant nucleophilic attack on the beta-phosphate. This complexity of the desulfurization reaction, however, does not affect the stereochemical integrity of the product but rather causes a minor dilution with nonchiral species. The usefulness of the (Sp)-2'-deoxyadenosine 5'-O-[1-17O,1-18O,1,2-18O]triphosphate in determining the stereochemical course of deoxyribonucleotidyl-transfer enzymes is demonstrated by using it to delineate the stereochemical course of the 3'----5'-exonuclease activity of DNA polymerase I. Upon incubation of this oxygen-chiral substrate with Klenow fragment of DNA polymerase I in the presence of poly[d(A-T)] and Mg2+, a quantitative conversion into 2'-deoxyadenosine 5'-O-[16O,17O,18O]monophosphate was observed. The stereochemistry of this product was determined to be Rp. Since the overall template-primer-dependent conversion of a deoxynucleoside triphosphate into the deoxynucleoside monophosphate involves incorporation into the polymer followed by excision by the 3'----5'-exonuclease activity and since the stereochemical course of the incorporation reaction is known to be inversion, it can be concluded that the stereochemical course of the 3'----5'-exonuclease is also inversion.
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PMID:Stereochemical course of the 3'----5'-exonuclease activity of DNA polymerase I. 609 2

1. To study the effects of maternal alcohol ingestion on brain parameters in offspring, rats were given ethanol for drinking (25% w/v) from the time of mating until sacrifice. Controls drank tap water. 2. Alcohol ingestion reduced daily food and liquid consumption but total caloric intake was only slightly diminished. 3. Maternal body weight increased and offspring body weight, size and brain weight were reduced in the animals receiving alcohol. 4. Brain concentrations of tryptophan, tyrosine and GABA were augmented in ethanol treated mothers at 1 day post-partum. 5. Comparison of brain parameters in offspring of alcoholic mothers with those of controls showed that tryptophan and 5HT concentrations were augmented in 4 day old neonates, NA was increased in 21 day fetuses and 1 day old neonates, and adenylate cyclase activity was also greater in the brains of 21 day fetuses and the cerebellums of 4 day old neonates. 6. Neither phosphodiesterase nor cyclic-AMP concentrations differed in offspring of alcoholic and control mothers. 7. Data showed alterations in brain NA and 5HT systems in the offspring of alcoholic mothers.
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PMID:Effects of maternal ethanol ingestion on cerebral neurotransmitters and cyclic-AMP in the rat offspring. 612 83

Domes are formed in large numbers by primary cultured monolayers of type II alveolar epithelial cells from rat lungs. These fluid-filled structures are formed by active transport of solute from medium to substratum, with water following passively. In the present study, we used dome-forming monolayers to study the regulation of alveolar epithelial transport processes by determining the effects on dome formation of adenosine 3',5'-cyclic monophosphate (cAMP) analogues, phosphodiesterase inhibitors, neurotransmitters, and vasopressin (antidiuretic hormone, ADH). The cAMP analogues (dibutyryl cAMP and 8-bromo-cAMP) and phosphodiesterase inhibitors (theophylline, papaverine, and isobutylmethylxanthine) caused large increases in dome formation by 24 h. ADH and beta-adrenergic agonists (epinephrine, terbutaline, and isoproterenol) also caused significant increases in dome density. The beta-agonist response was completely eliminated in the presence of the beta-blocker propranolol. Dibutyryl guanosine 3',5'-cyclic monophosphate and acetylcholine (cholinergic agonist) had no effect on dome formation, whereas the alpha-adrenergic agonist methoxamine caused a small but significant decrease in dome formation. These findings suggest that the active solute flux resulting in dome formation by type II alveolar epithelial cell monolayers is increased by substances expected to elevate intracellular cAMP (or analogue) concentrations. An attractive speculation having major implications for lung fluid balance is that transepithelial fluxes can be modulated by endogenous, and perhaps exogenous, chemical agents in adult mammalian alveolar epithelium in vivo.
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PMID:Regulation of transport across pulmonary alveolar epithelial cell monolayers. 614 12

Mineralo- and glucocorticoid-deficient states, such as Addison's disease, are partly characterized by an inability to generate a maximally concentrated urine. The purpose of the present study was to develop a model of adrenal insufficiency and to determine whether changes in the intrinsic function of the collecting duct could partly account for this concentrating defect. Two kinds of experiments were performed: an assessment of the in vivo ability of adrenal-ectomized rabbits to concentrate their urine, and an examination of the intrinsic hydroosmotic responsiveness of in vitro perfused collecting ducts isolated from normal and adrenalectomized rabbits. The present study demonstrates that adrenalectomized rabbits are unable to concentrate their urine maximally, and that the in vivo administration of either deoxycorticosterone, 250 mug/kg, or dexamethasone, 50 mug/kg, restored to or toward normal their concentrating ability. When cortical collecting tubules from adrenalectomized rabbits were perfused in vitro, they demonstrated a markedly blunted hydroosmotic response to antidiuretic hormone (ADH), which was corrected by the in vitro addition of either aldosterone (50 pM) or dexamethasone (50 pM), but not progesterone (50 pM). The steroids by themselves, in the absence of ADH, had no intrinsic effect on the water permeability of the collecting duct. The blunted hydroosmotic response across cortical collecting tubules from adrenal-ectomized rabbits was corrected by the addition of either 8-bromo cyclic AMP or a potent phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. The present studies show that the cortical collecting tubules obtained from adrenalectomized rabbits do not respond normally to ADH. The poor hydroosmotic response to ADH was corrected by exogenous aldosterone, dexamethasone, an analog of cyclic AMP, or a phosphodiesterase inhibitor. In conclusion, the present studies are consistent with the view that the concentrating defect seen in adrenal insufficiency is at least partly the result of the absence of the permissive effect that adrenal steroids exert on the ADH-induced reabsorption of water across the collecting duct. The absence of adrenal steroids results in a diminished rate of cyclic AMP accumulation in the cells of the collecting duct, either as a result of an augmented activity of cyclic AMP phosphodiesterase or a diminished rate of cyclic AMP generation.
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PMID:Urinary concentrating defect of adrenal insufficiency. Permissive role of adrenal steroids on the hydroosmotic response across the rabbit cortical collecting tubule. 615 51

Further studies of insulin secretion from isolated pancreatic islets of the NZO strain of obese hyperglycemic mouse have shown markedly impaired insulin secretory responses to D-glucose in islets from fasted or fed mice. NZO islets at a low glucose concentration (3.3 mM) showed a significant insulin secretory response to 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, but in the presence of this agent showed no significant additional response to increased glucose concentration. This contrasted with the situation in islets from an arbitrarily chosen control strain of mouse (C57Bl) which showed a small or insignificant response to 0.5 mM IBMX at a low glucose concentration, but a greatly enhanced response to glucose in the presence of IBMX. In contrast to the relative refractoriness of the NZO islets to glucose, they showed a large response to D,L-glyceraldehyde, at least equal to that found in the control islets. Glucose utilization was studied by measuring the conversion of D-[5-3H]glucose to [3H]H2O. In islets from both fasted and fed NZO mice, glucose utilization, when calculated on the basis of islet DNA content, was markedly reduced at high glucose concentrations compared to that in islets from the control strain. It is concluded that the relative unresponsiveness of NZO islets to glucose is associated with, and perhaps due to, a decreased rate of glucose utilization. The preserved responsiveness to glyceraldehyde suggests that the reduced glucose utilization may be due to a partial metabolic block before the triose phosphate step in the islet glycolytic pathway.
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PMID:Glucose utilization in relation to insulin secretion in NZO and C57Bl mouse islets. 615 4

Water-soluble proteins were extracted from individual retinas, optic nerves, combined optic tracts and lateral geniculate bodies, and superior colliculi of rabbits at 1, 3, and 18 days after injection of [3H]leucine into the right eye. The Ca2+-dependent protein modulator of 3':5'-cyclic-AMP phosphodiesterase (calmodulin) was isolated from these samples by a two-step polyacrylamide gel electrophoresis procedure. An analysis of the radioactivity incorporated into the total soluble proteins and the calmodulin revealed that most of the calmodulin was axonally transported at a slow rate (2--4 mm/day) and represented about 0.45% of the total transported soluble protein.
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PMID:Axonal transport of the Ca2+-dependent protein modulator of 3':5'-cyclic-AMP phosphodiesterase in the rabbit visual system. 616 Dec 17

The hypothesis that dioctyl sodium sulfosuccinate (DSS) induces intestinal fluid accumulation by inhibiting Na,K-ATPase activity and/or by increasing mucosal prostaglandin E2 (PGE2) content was tested in rats. Eighteen hours after its intragastric administration, DSS (260 mg/kg body weight) significantly decreased jejunal and colonic Na,K-ATPase activity--22.0 1.8 (SE) and 25.1 +/- 3.3 compared with 42.1 +/- 1.6 and 37.0 +/- 2.9 mumol . mg protein-1 . h-1, respectively, in saline-treated rats. DSS increased jejunal and colonic PGE2 content--155 +/- 15 (SE) and 273 +/- 40, compared with 109 +/- 9 and 175 +/- 23, pg/mg wet weight, respectively, in control rats. Although jejunal adenylate cyclase and phosphodiesterase activities were not affected by DSS (520 mg/kg body weight), they were significantly stimulated in the colon. Mucosal cyclic AMP content was similar in rats treated with DSS and saline. Patchy histological changes confined to surface absorptive cells were induced by DSS in both the jejunum and the colon. These findings suggest that inhibition of intestinal Na,K-ATPase activity and increase in mucosal PGE2 content might contribute to the net water accumulation induced in the rat intestine by DSS.
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PMID:Effect of dioctyl sodium sulfosuccinate on cyclic AMP and prostaglandin E2 contents, and Na,K-ATPase, adenylate cyclase and phosphodiesterase activities in rat intestine. 616 3


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