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 preferential adrenergic receptor antagonists to uninephrectomized rats revealed the beta 2-adrenergic mediation in diamine oxidase activity increase that occurs in the remaining kidney undergoing compensatory hypertrophy. In fact, beta 1, beta 2- or beta 2, but not alpha 1-, alpha 2-, or beta 1-receptor-blocking agents prevented this enzyme enhancement. Further studies with adrenoceptor agonists, such as epinephrine (alpha 1, alpha 2, beta 1, beta 2), isoproterenol (beta 1, beta 2) or terbutaline (beta 2) showed that also in normal rat kidney diamine oxidase activity is under the control of catecholamine-beta 2-receptors through a mechanism that involves new synthesis of mRNA and protein. Theophylline, an inhibitor of phosphodiesterase, or forskolin, an activator of adenyl cyclase, increased diamine oxidase activity as does epinephrine or nephrectomy. Thus, catecholamine-triggered beta 2-receptors coupled to adenyl cyclase are involved in the regulation of diamine oxidase activity in normal and hypertrophic rat kidney.
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PMID:Regulation of diamine oxidase expression by beta 2-adrenoceptors in normal and hypertrophic rat kidney. 286 Sep 26

Chronic administration of the beta-adrenergic receptor agonist isoproterenol (5 mg/200 g animal for 10 days) resulted in rat parotid and submandibular gland hypertrophy, and it induced synthesis of a series of proline-rich proteins (PRPs) and glycoproteins. Treated parotid glands additionally exhibit an increase in activity for the Golgi membrane enzyme UDP-galactose; N-acetylglucosamine 4 beta-galactosyltransferase. A series of beta-receptor agonists and phosphodiesterase inhibitors were examined for their abilities to influence salivary gland protein biosynthesis in a fashion similar to that observed with chronic isoproterenol treatment. beta 1/beta 2-Adrenergic-receptor agonists exhibited the greatest effects on parotid gland hypertrophy and PRP biosynthesis. These beta-agonists were also able to increase 4 beta-galactosyltransferase activity, but they did not promote the synthesis of a 220,000 dalton glycoprotein. Terbutaline (beta 2-receptor agonist) induced parotid gland hypertrophy but was only able to induce protein biosynthesis at higher drug concentrations. Finally, methoxyphenamine was unable to produce the observed changes in protein synthesis even at increased drug dosages. The phosphodiesterase inhibitors (theophylline and caffeine) were able to induce de novo PRP biosynthesis at drug doses of 20 mg/200 g animal. However, while causing mild gland hypertrophy, there was no observable change in 4 beta-galactosyltransferase activity with either phosphodiesterase inhibitor. This same regimen of beta-receptor agonists was unable to induce submandibular gland hypertrophy, PRP or glycoprotein biosynthesis in the same animals. This was also true for the two phosphodiesterase inhibitors. Co-injection of a beta 1 antagonist along with isoproterenol blocked the above protein changes in both the submandibular and parotid glands, suggesting that the stimulation of protein synthesis takes place by beta 1-type receptors on the gland cell surfaces.
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PMID:Analysis of protein synthesis in rat salivary glands after chronic treatment with beta-receptor agonists and phosphodiesterase inhibitors. 286 70

In the search for new effective positive inotropic agents for the treatment of congestive heart failure (CHF), interest has focused mainly on two groups of agents namely adrenoceptor agonists and drugs inhibiting phosphodiesterase. Common for drugs belonging to both groups is that their positive inotropic effects seem to involve an increase in the intracellular concentration of cyclic AMP. Drugs acting by stimulation of beta 1- and/or beta 2-adrenoceptors (e.g. dopamine, dobutamine, prenalterol, pirbuterol, salbutamol, terbutaline, fenoterol) have initial beneficial effects, but seem to be ineffective for long-term treatment. This has been suggested to be due to desensitization of the beta-adrenoceptors, and means, if this effect can be definitely established, that beta-adrenoceptor stimulation should be restricted to the acute treatment of CHF. Among drugs inhibiting phosphodiesterase, sulmazole, amrinone, milrinone, and fenoximone all have been shown to improve cardiac performance in patients with CHF during short-term treatment. However, results of long-term treatment with most of these drugs seem less encouraging. It has been suggested that these drugs may not be an effective approach to treatment of patients with CHF, since even if it is possible to achieve short-term gains, the long-term effects on the myocardium may be detrimental. Their ultimate place in the treatment of CHF remains to be established.
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PMID:Some new positive inotropic agents. 287 92

The time course of the effects of isoprenaline (3 X 10(-7) mol/l) on contractile force and on the cyclic AMP level was studied in the electrically driven isolated muscle strip of the human right atrium. Isoprenaline produced a rise in cyclic AMP content (maximum increase after 60 s) preceding the increase in contractile force. The effects of isoprenaline on contractile force and on the intracellular level of cyclic AMP were enhanced in the presence of the phosphodiesterase inhibitor papaverine (10(-5) mol/l). On the other hand, the beta-adrenoceptor antagonist propranolol (10(-7) mol/l) suppressed isoprenaline-induced cyclic AMP increases, but reduced the increase in force of contraction by only 35%. In addition, both the beta 1-selective antagonist bisoprolol (3 X 10(-9)-3 X 10(-8) mol/l) and the beta 2-selective antagonist ICI 118,551 (3 X 10(-9)-3 X 10(-8) mol/l) inhibited the isoprenaline-induced cyclic AMP increase concentration-dependently; ICI 118,551 produced more pronounced inhibition than bisoprolol. It is concluded that cyclic AMP is involved in the positive inotropic action of isoprenaline evoked by beta 1- and beta 2-adrenoceptor stimulation in isolated human right atrium; however, an additional cyclic AMP independent mechanism cannot be ruled out.
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PMID:The role of cyclic AMP in the positive inotropic effect mediated by beta 1- and beta 2-adrenoceptors in isolated human right atrium. 288 23

Plasmids containing sequences 3' of the adult beta 1 globin gene of Xenopus laevis are unstable on propagation in a range of E. coli host strains. Up to 300 bp of Xenopus DNA are lost by rec A independent recombination between (AT)37 and (AT)17 sequences. Additionally, smaller deletions occurring in or around the (AT)37 sequence are observed. Deletion of these potential cruciform structures occurs in the absence of exonuclease I, exonuclease V and exonuclease VIII as the same pattern of deletion events is observed in recA recBC sbcB and recBC sbcA recE strains.
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PMID:RecBC, sbcB independent, (AT)n-mediated deletion of sequences flanking a Xenopus laevis beta globin gene on propagation in E. coli. 301 63

Effects of the new selectively beta 1-adrenergic cardiotonic drug denopamine (TA-064), (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, on the adenylate cyclase-adenosine-3',5'-monophosphate (c-AMP) system of various tissues and cells in rats and guinea pigs were investigated in comparison with those of isoproterenol. Denopamine at concentrations above 10(-6) M stimulated lipolysis in vitro, and, above 10(-5) M, elevated the c-AMP level in isolated rat fat cells. The c-AMP level of guinea-pig heart ventricular muscle was also elevated when the heart was perfused with 3 X 10(-6) M denopamine or when slices of ventricular muscle were incubated with 10(-6) M denopamine. These changes were abolished in the presence of beta-adrenergic antagonists. Incubation with denopamine did not cause substantial elevation of c-AMP levels in rat reticulocytes and diaphragm. Denopamine activated adenylate cyclase of the rat cell membranes in a concentration-dependent manner. Although dose dependence was less apparent, denopamine also activated adenylate cyclase of the membrane fraction from guinea pig cardiac muscle, but it hardly activated the same enzyme from rat reticulocytes. Isoproterenol, on the other hand, showed marked concentration-dependent activation of adenylate cyclase in all these preparations. Denopamine did not inhibit c-AMP phosphodiesterase of both particulate and supernatant fractions of guinea-pig cardiac muscle. The stimulation of lipolysis by denopamine was observed even when elevation of the c-AMP level was not detected, while the stimulation of lipolysis by isoproterenol was always accompanied with an elevation of c-AMP. When guinea-pig hearts were perfused with 3 X 10(-6) M denopamine or 10(-7) M isoproterenol, their cardiotonic effects were of the same magnitude whereas the degree of c-AMP elevation in the ventricular tissue by denopamine was significantly less than that by isoproterenol. It was concluded that stimulation of the adenylate cyclase-c-AMP system by denopamine was restricted to the tissues whose receptors were predominantly of the beta 1-type, and that the elevation of c-AMP levels in these tissues by denopamine was less marked than by isoproterenol, suggesting that the stimulation of lipolysis and heart by denopamine may be mediated by a special pool of c-AMP or some other unknown factor(s).
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PMID:Beta 1-adrenergic selectivity of the new cardiotonic agent denopamine in its stimulating effects on adenylate cyclase. 303 56

In previous studies we reported that immunization of mice with ungulate insulins induced the development of antiinsulin antibodies, which include an idiotype that appeared to recognize the part of the insulin molecule recognized by the hormone receptor. The antiinsulin antibodies of this idiotype were replaced spontaneously by antiidiotypic antibodies. The antiidiotypic antibodies, which persisted for about 14 d, mimicked insulin and functioned as antibodies to the insulin receptor. They induced down regulation, desensitization and refractoriness of the insulin receptor and disturbances in glucose homeostasis in vivo (Shechter, Y., D. Elias, R. Maron, and I.R. Cohen., 1984; Elias, D., R. Maron, I.R. Cohen, and Y. Shechter. 1984, J. Biol. Chem. 259: 6411-6419). We now report that effects of the antiidiotypic antibodies on the insulin receptor effector system can be modified pharmacologically. Administration of the beta-adrenergic agonist isoproterenol during the period of insulin resistance (days 26-40 after primary immunization), largely restored fat cell responsiveness to insulin, and eliminated the appearance of fasting hyperglycemia. This restoration appeared to be caused by inhibition of both insulin receptor desensitization and refractoriness. In contrast, down regulation of insulin receptors was not reversed by isoproterenol treatment in vivo. The effects of treatment with isoproterenol persisted for 2-4 d after termination of treatment. The beta-antagonist, propranolol and more so, the beta 1a-antagonist metoprolol, specifically blocked the effect of isoproterenol at a molar ratio of 3-10:1. Oral administration of the cAMP phosphodiesterase inhibitor, aminophylline, was also effective in inhibiting the development of desensitization in fat cells. These results indicate that treatment with beta 1-adrenergic agonists in vivo, or other agents that elevate cellular cAMP levels, can inhibit the development of the "postbinding" defects induced by insulin-mimicking, antireceptor antibodies. These observations have both basic and clinical implications.
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PMID:Desensitization of the insulin receptor by antireceptor antibodies in vivo is blocked by treatment of mice with beta-adrenergic agonists. 329 Feb 58

An enzyme system catalyzing the synthesis of the beta 1,2-linked glucan backbone of the membrane-derived oligosaccharides of Escherichia coli from UDP-glucose has an essential requirement for the E. coli acyl carrier protein (ACP). This finding was surprising, because all other characterized functions of ACP involve acyl thioester residues linked to the phosphopantetheine moiety covalently bound to ACP. We now report that the activity of ACP in the synthesis of membrane-derived oligosaccharides is not altered by treatment with the sulfhydryl reagent N-ethylmaleimide nor by complete removal of the phosphopantetheine residue by treatment with a specific phosphodiesterase. The function of ACP in the synthesis of membrane-derived oligosaccharides is thus clearly different from that involved in lipid biosynthesis. We have nevertheless found that the same molecular species of ACP that undergo enzymic acylation with long-chain fatty acid residues also function in the synthesis of membrane-derived oligosaccharides.
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PMID:The function of acyl carrier protein in the synthesis of membrane-derived oligosaccharides does not require its phosphopantetheine prosthetic group. 347 86

Topically administered salbutamol was extremely effective in suppressing immediate allergic conjunctivitis in the guinea pig; a dose as low as 0.1% elicited 98% inhibition. Topical pretreatment with 1% propranolol completely blocked the suppressant action of 0.1% salbutamol. This was also the case after systemic propranolol (1 mg/kg SC); the beta-adrenoceptor antagonist itself has no effect on antigen-induced inflammation. The effect of 0.1% salbutamol was unaltered by pretreatment with the specific beta 1-adrenoceptor antagonist betaxolol (1 mg/kg SC). In marked contrast, the suppressant action of 0.1% salbutamol was profoundly inhibited by pretreatment with the selective beta 2-adrenoceptor antagonist ICI-118,551 (0.5 mg/kg SC). The experiments employing beta-adrenoceptor antagonists unequivocally demonstrate that the salbutamol suppression of immediate allergic conjunctivitis in the guinea pig is mediated via the activation of beta 2-adrenoceptors. The methylxanthine phosphodiesterase inhibitor theophylline was active after oral administration, 50 mg/kg eliciting an 80% inhibition. Theophylline was inactive topically at 1% and 5%, but this could be due to the fact that the compound was insoluble at these concentrations. Thus, procedures that elevate cyclic-AMP levels suppress immediate hypersensitivity reactions in the guinea pig conjunctiva. Whether or nor this offers an alternative approach to treat allergic conjunctivitis in humans remains to be determined.
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PMID:The ability of salbutamol and theophylline to suppress immediate allergic conjunctivitis in the guinea pig. 366 75

The technique of electrical field stimulation (e.f.s.) was employed in conjunction with selective pharmacological antagonists to specifically investigate the role of endogenous neurotransmitter(s) in the activation of beta-adrenergic receptor mechanisms in isolated parotid gland segments of the rat. The field-stimulus-induced amylase release due to beta-adrenergic receptor activation was characterized as that persisting in the presence of atropine (10(-5) M) and phentolamine (10(-5) M) and susceptible to blockade by propranolol (5 X 10(-6) M), i.e. combined beta 1- and beta 2-receptor blockade. The selective beta 1-receptor antagonist metoprolol (10(-5) M) was as effective as propranolol in blocking the beta-mediated enzyme release. The selective beta 2-receptor antagonist, H35/25 (10(-5) M) did not significantly affect the field-stimulus-induced amylase release. In the absence of any phosphodiesterase inhibitor the levels of cyclic AMP in the tissues were close to the limit of detection. Field stimulation was however associated with a fourfold increase in cyclic AMP. By comparison isoprenaline (10(-5) M) gave rise to a tenfold increase in cyclic AMP. The changes in cyclic AMP metabolism, in response to both field stimulation and isoprenaline, were greatly enhanced in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The field-stimulus-induced increase in cyclic AMP was abolished by the beta 1-adrenergic receptor antagonist, metoprolol, but persisted in the presence of the beta 2-adrenergic antagonist, H35/25. IBMX was found to have a potent direct effect on amylase release. IBMX (10(-3) M) also gave rise to a tenfold increase in cyclic AMP. IBMX is then as effective as 10(-5) M-isoprenaline in stimulating both enzyme secretion and cyclic AMP metabolism. The secretory response to IBMX was unaffected by beta-adrenergic blockade by propranolol, was independent of extracellular calcium and did not give rise to 86Rb+ efflux. Importantly, isoprenaline (10(-5) M) failed to evoke any significant increase in amylase release if introduced during sustained superfusion of IBMX, yet it is in such protocols that the greatest changes in cyclic AMP metabolism are seen. The study clearly demonstrates that the beta-adrenergic-receptor-regulated amylase release in response to nerve stimulation is mediated predominantly, if not exclusively, by the beta 1-receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Beta-adrenergic receptor mechanisms in rat parotid glands: activation by nerve stimulation and 3-isobutyl-1-methylxanthine. 608 58


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