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)

The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. beta-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 mumol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol. The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.
...
PMID:The role of cyclic adenosine monophosphate in adrenergic effects on ventricular vulnerability to fibrillation in the isolated perfused rat heart. 20 34

The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [(3)H]cyclic AMP after labeling of the islets with [2-(3)H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [(3)H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [(3)H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media. The [(3)H]cyclic AMP response to glibenclamide was influenced by prior exposure of the islets to glucose, a 30-min preincubation with 27.7 mM glucose, enhancing the response to the sulfonylurea over a subsequent 5-min stimulation period. Sulfonylureas exerted their effects at low but not at high glucose concentrations, i.e., shifted the glucose dose-response curve to the left both for [(3)H]cyclic AMP accumulation and insulin release. On the other hand, increasing concentrations of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, progressively augmented the effects of the drugs. Omission of Ca(++) from the incubation media inhibited both the glucose and the sulfonylurea [(3)H]-cyclic AMP and insulin responses. Epinephrine (1 muM) partially inhibited the [(3)H]cyclic AMP response to both glucose and sulfonylurea, whereas insulin release was completely abolished. It is concluded that the sulfonylurea effects on islet cyclic AMP are intimately related to those of glucose. It is suggested that sulfonylureas exert a major part of their action by facilitating the effect of glucose on the beta-cell adenylate cyclase; the increased cyclic AMP level, in its turn, enhances the secretion rate of insulin.
...
PMID:Interacting effects of sulfonylureas and glucose on cyclic AMP metabolism and insulin release in pancreatic islets of the rat. 20 36

Adipocytes isolated from normal, hypothyroid, and hyperthyroid rats were characterized with respect to their lipolytic activity (assessed by glycerol release) and beta-adrenergic receptors (assessed by binding of (--) [3H]alprenolol). Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals. Adipocytes from hypothyroid rats were unresponsive to epinephrine in a concentration range of 0.1-10 micron, with moderate responses at higher concentrations; injection of T3 in hypothyroid rats restored lipolytic responsiveness of the adipocytes to normal levels. Quabain (1 mM) inhibited lipolytic responses to epinephrine by 40--45% in normal and hyperthyroid rats; the lipolytic increment due to the hyperthyroid state was uninfluenced by ouabain. The lipolytic refractoriness to epinephrine of hypothyroid adipocytes was restored to normal levels by theophylline (1 mM) or EGTA (1 mM); the theophylline and EGTA effects were not additive, suggesting that they stimulated lipolysis via a common mechanism. Epinephrine-induced lipolysis in all groups was progressively inhibited by increasing concentrations of Ca2+ in the medium. The Ca ionophore, A23187, showed a concentration-dependent inhibitory action. Theophylline (1mM) almost completely overcame the inhibitory action of the ionophore; in the presence of lower concentrations of theophylline, the inhibitory effect of the ionophore was least in hypothyroid and greatest in hyperthyroid fat cells. The findings suggest that the differences in the lipolytic response to epinephrine observed in hyperthyroid, euthyroid, and hypothyroid adipocytes are not due to alterations in the number or affinity of beta-adrenergic receptors nor to a membrane mechanism that might show differential ouabain sensitivity, but may be related to altered cellular Ca2+ concentrations which may indirectly alter cellular phosphodiesterase activity.
...
PMID:Thyroid hormone modulation of epinephrine-induced lipolysis in rat adipocytes: a possible role of calcium. 21 6

The biochemical characteristics of cyclic 3',5'-nucleotide phosphodiesterase were studied in homogenates of male albino rat skin using preparations which were predominantly epidermal. Enzymatic activity was detected in both the particulate and soluble fractions of these skin homogenates. Two kinetically distinct phosphodiesterase (PDE) activities were detected in the soluble fraction (100,000 times g supernatant). This 100,000 times g supernatant contains at least two distinct protein bands that hydrolyze cyclic AMP as demonstrated by gel electrophoresis. Divalent cations (Mg-++ or Mn-++) and 2-mercaptoethanol were required for maximal enzymatic activity. Epinephrine, dibutyryl cyclic AMP, and methylxanthines inhibited while imidazole and histamine phosphate stimulated the cyclic AMP phosphodiesterase activity at high and low cyclic AMP concentrations. Cyclic GMP competitively inhibited hydrolysis of low, but not high, concentrations of cyclic AMP. Hydrocortisone phosphate in pharmacologic concentrations blocked PDE denaturation by heat. These studies indicate that there are complex interrelationships between cyclic nucleotides and PDE in rat skin.
...
PMID:Cyclic 3',5'-nucleotide phosphodiesterase in rat skin. II. Biochemical characterization. 23 64

The effect of various hormones and drugs on the adenyl cyclase system of pig and human epidermal slices was studied in vitro. Adrenaline and isoproterenol in the presence of theophylline increased the epidermal cyclic AMP level 20-fold in 5 min. Noradrenaline also stimulated cyclic AMP accumulation but to a much lesser degree. The adrenaline stimulation was marked even in the absence of the phosphodiesterase inhibitor, theophylline. Theophylline potentiated the effect of adrenaline at the concentration of 2-10 mM although theophylline alone did not elevate the cyclic AMP level significantly. The Km for adrenaline stimulation of the adenyl cyclase system of pig epidermis was 7-7 X 10(-7) M. A beta-adrenergic antagonist, propranolol, markedly inhibited the adrenaline stimulation while alpha-antagonists, phentolamine or priscoline, showed little effect. The results are in accord with the view that the epidermis possesses an active adenyl cyclase system with beta-adrenergic receptors.
...
PMID:The effects of catecholamine and related compounds on the adenyl cyclase system in the epidermis. 119 26

Adrenaline, permeable cyclic adenosine monophosphate (cAMP) derivatives and insulin are known to elicit an increase in quantal size at the frog neuromuscular junction, primarily by increasing the amount of acetylcholine (ACh) per quantum. The quantal size increases produced by adrenaline or cAMP were antagonized by the protein kinase inhibitor H8 N-[2-(methylamino)ethyl]-5-isoquinolonesulfonamide. The increase in quantal size produced by insulin was not prevented by H8. Quantal size is also increased by pretreatment in hypertonic solution; this increase was also antagonized by H8. The H8 did not alter the increase in miniature endplate potential (MEPP) frequency produced by the hypertonic solution. A permeable cGMP derivative had no effect on quantal size. The diastereomer (Sp)-cAMPS (cyclic 3',5'-phosphothoate) activates protein kinase A(PKA). It elicited an increase in quantal size. The (Rp)-cAMPS isomer is known to inhibit PKA; it had no effect on quantal size. The increase in quantal size produced by hypertonic solution was antagonized by (Rp)-cAMPS but not by (Sp)-cAMPS. Brief exposure to a hypertonic solution containing a phosphodiesterase inhibitor followed by incubation in the inhibitor leads to an increase in quantal size. We conclude that one pathway for signaling for an increase in quantal size involves activation of PKA and that hypertonic pretreatment acts via this pathway.
...
PMID:Effects of activators and inhibitors of protein kinase A on increases in quantal size at the frog neuromuscular junction. 137 90

Inotropic support is often required for post-operative management of patients following mitral valve operation. The use of positive inotropes is limited by tolerance development and increase in myocardial oxygen demand. We have compared i.v. enoximone (E) (group E, n = 13), a recently developed phosphodiesterase (PDE) inhibitor, to the conventional i.v. therapeutics dopamine (D) and glyceroltrinitrate (G) in patients following mitral valve operation. The two groups were comparable in terms of physical and pre-operative haemodynamic data. Haemodynamic measurements including cardiac index (CI) determinations were recorded for the first 18 h post surgery in both groups. Group E received a bolus of 1 mg.kg-1 E followed by 4-20 micrograms.kg-1.min-1 (mean = 5 +/- 2 micrograms.kg-1.min-1) for 14 h according to therapeutic requirements, while group D received dopamine (4-10 micrograms.kg-1.min-1, mean = 3.8 +/- 1.9 micrograms.kg-1.min-1) and glyceroltrinitrate (0.5-5 micrograms.kg-1.min-1; mean = 4 +/- 2 micrograms.kg-1.min-1). Adrenaline was added if the MAP was below 60 mmHg or the CI was below 2.5 in both groups (range 50-500 ng.kg-1.min-1; mean E = 0.7 +/- 2 ng.kg-1.min-1; mean D = 2 +/- 2.8 ng.kg-1.min-1). Bolus injection of E resulted in a rise in CI from 2.6 to 3.21.min-1.m-2 (P less than 0.05) within 30 min, followed by a further rise to a maximum of 3.51.min-1.m-2 6 h post bolus. Termination of the E drip resulted in a drop of CI to baseline values (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Enoximone, a post-operative inodilator in patients following mitral valve operation: a prospective and controlled study. 153 88

Epinephrine (EPI) is lipolytic and insulin (INS) antilipolytic in the isolated fat cell (IFC). We have previously demonstrated that in a perifusion system the antilipolytic action of INS is more powerful when IFC are exposed to INS before EPI. In contrast to their opposite effects on lipolysis, both INS and EPI stimulate low-Km cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) in adipose tissue. In view of these observations, we decided to determine the effects of sequential addition of EPI and INS on stimulation of PDE from rat adipose tissue. Using previously published methods, the effects of INS and EPI on PDE were assessed alone, together with INS followed by EPI, and then with EPI followed by INS. The resulting data demonstrate that EPI and INS individually both stimulate PDE (P less than .001); EPI plus INS together stimulate PDE minimally compared with EPI or INS alone (P less than .001); when adipose tissue is included with INS first, then followed by EPI, activation of PDE is much less than INS or EPI alone (P less than .001); and when adipose tissue is stimulated by EPI then INS, there is no activation of PDE, different from EPI or INS alone (P less than .001). In conclusion, in perifused IFC, INS and EPI always oppose each other. In studies using activation of PDE, EPI and INS each stimulate PDE, but INS opposes EPI when incubated simultaneously. When adipose tissue is incubated first with INS followed by EPI, PDE is activated. In contrast, when the reverse order is applied, no activation of PDE is observed.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of sequence and timing of hormonal additions on adipose tissue: activation of low-Km cyclic adenosine monophosphate phosphodiesterase. 165 98

Autophagy is a non-selective bulk process for degradation of cytoplasm, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lifes. The initial autophagic sequestration step is subject to feedback inhibition by amino acids, an effect which is potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive, alpha 1-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid. Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy in a differential (ligand-dependent) manner, and that amphisomes may play a central role as collecting stations for material destined for lysosomal degradation.
...
PMID:Hepatocytic autophagy. 166 81

Autophagic degradation of cytoplasm (including protein, RNA etc.) is a non-selective bulk process, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lives. The initial autophagic sequestration step, performed by a poorly-characterized organelle called a phagophore, is subject to feedback inhibition by purines and amino acids, the effect of the latter being potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive alpha 1-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid. Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, on intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy to a variable extent, and that the amphisome may play a central role as a collecting station for material destined for lysosomal degradation. Protein degradation can also take place in a 'salvage compartment' closely associated with the endoplasmic reticulum (ER). In this compartment unassembled protein chains are degraded by uncharacterized proteinases, while resident proteins return to the ER and assembled secretory and membrane proteins proceed through the Golgi apparatus. In the trans-Golgi network some proteins are proteolytically processed by Ca(2+)-dependent proteinases; furthermore, this compartment sorts proteins to lysosomes, various membrane domains, endosomes or secretory vesicles/granules. Processing of both endogenous and exogenous proteins can occur in endosomes, which may play a particularly important role in antigen processing and presentation. Proteins in endosomes or secretory compartments can either be exocytosed, or channeled to lysosomes for degradation. The switch mechanisms which decide between these options are subject to bioregulation by external agents (hormones and growth factors), and may play an important role in the control of protein uptake and secretion.
...
PMID:Autophagy and other vacuolar protein degradation mechanisms. 174 Jan 88


<< Previous 1 2 3 4 5 6 Next >>

---