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)

The administration of glycemia-affecting chemicals such as alloxan, streptozotocin, and 6-aminonicotinamide decreases the conversion ratio of tryptophan to niacin. Adrenalin is also known to increase the glucose level. For this reason, the effects of adrenalin on the conversion ratio were investigated. We found that the conversion ratio of tryptophan to niacin was reduced to half by the intraperitoneal injection of adrenalin at 75 micrograms/day/rat (body weight, about 250 g) every day for 7 days. Niacin decreases adrenalin-stimulated glycogenolysis via stimulating phosphodiesterase activity or depressing adenyl cyclase activity. Accordingly, in urgent need of energy, animals would have to decrease the concentration of niacin within the body.
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PMID:Effects of adrenalin on the conversion ratio of tryptophan to niacin in rats. 854 52

These studies were conducted to determine whether the alpha 2-agonists epinephrine and dexmedetomidine inhibit osmotic water permeability (Pf) and urea permeability (Pu) in the rat inner medullary collecting duct (IMCD). Wistar rat IMCD segments were perfused via standard methods, and Pf and Pu were determined in separate studies. The control period was followed by adding 220 pM arginine vasopressin (AVP) or 10(-4) M dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) to the bath. Epinephrine or dexmedetomidine, both at 1 microM, was then added to the bath, and this period was followed by adding 1 microM atipamezole, a selective alpha 2-antagonist. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was present in all experiments with DBcAMP. Epinephrine inhibited AVP- and DBcAMP-stimulated Pf by 90% and 80%, respectively. Dexmedetomidine inhibited AVP- and DBcAMP-stimulated Pf by 98% and 97%, respectively. Epinephrine inhibited AVP- and DBcAMP-stimulated Pu by 70% and 60%, respectively. Dexmedetomidine failed to affect Pu. Atipamezole reversed all inhibitory effects. These data confirm an alpha 2-mediated mechanism in the IMCD that modulates Pf and Pu, and they indicate that inhibition occurs via post-cAMP cellular events.
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PMID:Alpha 2-adrenergic-mediated inhibition of water and urea permeability in the rat IMCD. 876 Feb 56

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

Changes in the outflow facility of perfused calf eyes and in the shape of cells in cultured trabecular meshwork (TM) have been studied, following exposure to adrenergic agents and phosphodiesterase inhibitors (PDE). Dobutamine caused confluent TM cells to change their usual polygonal shape to a characteristic stellate shape. Salbutamol had no effect, but PDE inhibitors, isobutylmethylxanthine (IBMX), theophylline, and caffeine were very effective in producing this shape change. Epinephrine, isoproterenol, dobutamine, and salbutamol did not increase the outflow facility, either at 22 degrees C or 36 degrees C, while theophylline, caffeine, and IBMX did increase it in a dose-dependent manner. On the other hand, the high concentrations of beta-adrenergic agents required to produce even a small change in outflow facility and cell shape argue against the involvement of adrenergic-receptor mediation and may suggest another mechanism; on the other, the enhancement of epinephrine effects by PDE inhibitors and the similar effect produced by cyclic adenosine 3',5'-cyclic phosphate (cAMP) and purines suggest that changes in the cell shape are produced by beta-receptor activation. The beta-adrenergic agents were not effective in changing outflow facility, but the PDE inhibitors were remarkably effective both in changing the shape and in increasing facility.
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PMID:Effects of adrenergic agents and phosphodiesterase inhibitors on outflow facility and cell shape of bovine trabecular meshwork. 914 86

Epidermal growth factor (EGF) stimulates glycogenolysis in mouse liver, but the effect requires concentrations that are only achieved in plasma upon adrenergic stimulation of EGF release from submandibular salivary glands. Thus, we studied the interaction between adrenaline and EGF in liver glycogen metabolism, both in whole animals and in isolated hepatocytes. Adrenaline administered to anesthetized mice stimulated both the endocrine secretion of EGF from submandibular salivary glands and the degradation of glycogen in the liver. In sialoadenalectomized mice, adrenaline administration did not increase plasma EGF concentration. In these animals, the glycogenolytic response to adrenaline was enhanced. The sensitivity of hepatocytes to adrenaline was similar in cells from sialoadenalectomized and sham-operated mice. EGF, added to isolated hepatocytes, reduced the glycogenolytic effect of adrenaline (the maximal effect but not the ED50). Adrenaline stimulated glycogen degradation through both an alpha1-adrenergic mediated Ca2+ increase and a beta-adrenergic-mediated cAMP increase. EGF did not interfere with the rise of cytosolic Ca2+ but decreased the cAMP signal. EGF did not decrease the glycogenolytic effect of phenylephrine or VP (which increased cytosolic Ca2+ but not cAMP), but EGF decreased both the glycogenolytic effect and the cAMP signal generated by glucagon or forskolin. EGF did not interfere with the glycogenolytic effect of CPT-cAMP or bt2-cAMP. The effect of EGF on cAMP was blocked by 3-isobutyl-1-methylxanthine. These results demonstrate that the effect of EGF on the glycogenolytic action of adrenaline involves interference with the generation of the cAMP signal. We suggest that EGF induces such an effect through the activation of a phosphodiesterase.
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PMID:Interaction between adrenaline and epidermal growth factor in the control of liver glycogenolysis in mouse. 916 54

Changes in the outflow facility of perfused bovine eyes and in the shape of cells in cultured trabecular meshwork (TM) were studied after exposure to adrenergic drugs. Dobutamine, a selective beta 1 agonist caused confluent TM cells to change from their usual polygonal shape to a characteristic stellate shape. Salbutamol, a selective beta 2 agonist showed no effect. The phosphodiesterase (PDE) inhibitors, isobutylmethylxanthine (IBMX), theophylline, and caffeine were also very effective in producing this shape change. Epinephrine, isoproterenol, dobutamine or salbutamol did not increase the outflow facility, at temperatures of 22 degrees C or 36 degrees C, whereas theophylline, caffeine and IBMX increased the facility in a dose-dependent manner. The high concentrations of beta-adrenergic agents required to produce even a small change in outflow facility and the cell shape argue against the involvement of adrenergic receptor mediation; on the other hand, the enhancement of the effects of epinephrine by PDE inhibitors and a similar effect produced by cAMP suggest that the changes in the cell shape are produced by beta-receptor activation. The beta-adrenergic agents were ineffective on changing outflow facility but the PDE inhibitors were remarkably effective in producing both shape change and increasing facility. PDE inhibition has much greater influence on and around the outflow channels than pure beta-adrenergic agonists, at least in enucleated bovine eyes.
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PMID:[Effects of beta-adrenergic agonists and phosphodiesterase inhibitors on the outflow facility of the eye]. 925 15

Adrenaline, forskolin and ATP all evoked accumulation of cyclic AMP in equine sweat gland epithelial cells, although the response to adrenaline was more transient than that to forskolin and ATP. Cells preincubated in adrenaline (10 micromol l-1, 32 min) showed essentially complete, homologous desensitisation, and this phenomenon reversed slowly (half-time 6.3+/-0.9 h). After 10 min of recovery from preincubation in adrenaline, isobutylmethylxanthine (IBMX, 5 mmol l-1) had no effect upon the desensitisation and the cells showed no loss of sensitivity to ATP and forskolin. After 10 h, however, the persistent desensitisation was partially reversed by IBMX and the cells showed reduced responses to ATP and forskolin. Increased phosphodiesterase activity may thus contribute to the persistent desensitisation. Experiments using forskolin-preincubated (100 micromol l-1, 32 min) cells suggested that increased cytosolic cyclic AMP levels did not underlie the initial loss of sensitivity to adrenaline but that this second messenger may initiate the series of events leading to the generalised loss of sensitivity seen after 10 h.
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PMID:Persistent desensitisation of the beta 2 adrenoceptors expressed by cultured equine sweat gland epithelial cells. 940 14

Subarachnoid hemorrhage (SAH) is associated with impaired nitric oxide (NO)-mediated cerebral vasodilatation. We tested the hypothesis that SAH causes alterations in the production of, hydrolysis of, or responsiveness to cGMP in the rat basilar artery in vivo. Rats were injected with saline or autologous blood into the cisterna magna. Two days later, effects of vasoactive drugs on basilar artery diameter were examined using a cranial window preparation. Vasodilator responses to ACh, sodium nitroprusside (SNP), and low concentrations (</=10(-5) M) of zaprinast, an inhibitor of phosphodiesterase V (PDE V), were impaired in SAH rats (P < 0.05). In contrast, vasodilator responses to adenosine and 8-BrcGMP were similar in control and SAH rats. Vasoconstrictor responses to 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, were unaffected by SAH. In the presence of zaprinast (10(-5)-10(-4) M), responses to ACh and SNP were equivalent in control and SAH rats. Thus an increased rate of cGMP hydrolysis by PDE V may be a major factor contributing to the impairment of NO-mediated cerebral vasodilatation after SAH.
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PMID:Impaired cerebral vasodilator responses to NO and PDE V inhibition after subarachnoid hemorrhage. 1056 24

Maintenance of adequate oxygen balance to all tissues is one of the primary objectives when dealing with patients undergoing cardiac surgery. Cardiac output is one of the major components of oxygen delivery so that its maintenance is an important consideration. Due to pre-operative cardiac lesion and myocardial dysfunction secondary to the events related to cardiac surgery and cardiopulmonary by-pass, circulatory support by pharmacological or mechanical means is frequently required after surgery. Therefore, inotropes and vasodilators are used to improve the myocardial performance after cardiac surgery. Epinephrine, dopamine and dobutamine are commonly used inotropes. Dopexamine and phosphodiesterase inhibitors such as amrinone, milrinone and enoximone are some of the newer agents that have been introduced in clinical practice. Amongst the vasodilators, sodium nitroprusside and nitroglycerin are commonly used. Alpha adrenergic blockers such as phentolamine and phenoxybenzamine and calcium channel blockers such as diltiazem are some other vasodilators that can be used. Many units still regard epinephrine as an inotrope of choice and use its predominant beta agonist effect in the dose range of 0.02 to 0.04 mg/kg/minute. Some prefer dobutamine and others a combination of inotrope and vasodilator or an inodilator. Phosphodiesterase inhibitors can be useful in certain situations such as pre-existing ventricular dysfunction or when stunning of the myocardium is suspected with down regulation of beta receptors. Dopamine is useful in the renal vasodilating dose to improve renal perfusion and improve output. There is no ideal inotrope at present and each one has its own drawbacks. The clinician must learn to use the inotropes (especially the newer ones) based on his own clinical experience.
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PMID:Pharmacologic support of circulation in patients undergoing cardiac surgery. 1063 2

All involuntary innervated structures of the body are controlled by the sympathetic and parasympathetic nervous system. Adrenaline, noradrenaline and dopamine are endogenous catecholamines binding to adrenergic and dopaminergic receptors, respectively, to mediate their clinical effects. Adrenoceptors are classified as alpha 1, alpha 2, beta 1 and beta 2 subtypes which were even further subcharacterized the recent years. Adrenoceptors are membrane proteins interacting with the agonist and, thus, inducing G-protein mediated intracellular effects. Adrenaline induces an extensive increase of heart rate and stroke volume mediated by beta-adrenoceptors and significantly enhances peripheral vascular resistance by alpha-adrenoceptor stimulation, when administered beyond 0.1 microgram/kg.min. In contrast, the clinical effects of noradrenaline are predominantly characterized by alpha-adrenoceptor stimulation resulting in a less pronounced increase of heart rate. Dopamine, less potent on adrenoceptors, shows additional effects on renal as well as on splanchnic circulation mediated by dopaminergic receptors. Dobutamine, primarily acting on beta-adrenoceptors, results in positive inotropic effects without an increase in vascular resistance. Dopexamine, a synthetic catecholamine, induces vasodilation via beta 2-adrenoceptor stimulation and potentially increases splanchnic blood flow by additional effects on dopaminergic receptors. Isoproterenol, the classical beta-adrenoceptor agonist, mediates positive inotropic effects and causes a major increase in heart rate and a significant decrease of systemic vascular resistance. Independent on adrenoceptors, phosphodiesterase-III-inhibitors exert positive inotropic and vasodilating activity by an increase in intracellular cAMP concentration induced by inhibition of cAMP hydrolysis.
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PMID:[Principles of catecholamine therapy. 1. Characterization of clinically relevant sympathomimetics]. 1071 95


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