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 activity of 2-bromo-alpha-ergokryptine (bromocriptine) (5 mg kg-1, i.p.) on adenylate cyclase and on phosphodiesterase (PDE-PDE II) of rat striatum, has been examined both in vitro and in vivo. In vitro and in vivo bromocriptine stimulated adenylate cyclase activity, but reduced the stimulating effect of dopamine on adenylate cyclase activity. Bromocriptine showed a dose-dependent biphasic action on phosphodiesterases in vitro while in vivo it stimulated them. The results obtained proved bromocriptine to have an agonist-antagonist action at striatal dopamine receptor level, with a relevant effect on the cAMP system.
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PMID:Effects of bromocriptine on adenylate cyclase and phosphodiesterase activities of rat striatum. 2 11

As revealed by spectrophotometry, native but not heat-inactivated influenza virus in the presence of ATP reduced the activity of calcium-dependent regulator protein-stimulated 3',5'-c AMP-phosphodiesterase (CDR-PDE). ATP could be partially replaced by ADP but not by AMP. The degree of CDR-PDE inhibition increased with increasing virus concentration. But at very high virus concentrations the rate of 3',5'-c AMP hydrolysis by CDR-PDE was not linearly dependent on time. At appropriate virus concentrations the degree of inhibition of CDR-PDE activity remained unchanged for the whole reaction time.
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PMID:Role of calcium-dependent regulator protein (CDR) in inhibition of 3',5'-c AMP-phosphodiesterase by influenza virus. II. Kinetic studies on inhibition of CDR-dependent phosphodiesterase by influenza virus. 4 Apr 17

The effects of various agents on the newly identified cyclic CMP phosphodiesterase (C-PDE) in crude extracts of a number of rat tissues and on the enzyme partially purified from the rat liver were examined. Papaverine and 1-methyl-3-isobutylxanthine were without effects on C-PDE at concentrations that inhibited up to 90% of cyclic AMP phosphodiesterase (A-PDE) and cyclic GMP phosphodiesterase (G-PDE) activities. When assayed using 1 micron substrates, theophylline inhibited C-PDE to a lesser extent than A-PDE and G-PDE. 2'-Deoxy cyclic AMP (specific A-PDE inhibitor) and 2'-deoxy cyclic GMP (specific G-PDE inhibitor) were relatively poor and non-specific inhibitors for C-PDE. Imidazole, while augmenting the high Km A-PDE and G-PDE from the liver but not from the heart, was without effect on the liver C-PDE but stimulated the heart C-PDE. Potassium phosphate was more specific in inhibiting C-PDE than A-PDE and G-PDE. The present findings suggest that C-PDE represents a potential site of specific pharmacological regulations, and that C-PDE may be a separate enzyme distinguishable from the purine cyclic nucleotide class of phosphodiesterases.
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PMID:Effects of phosphodiesterase inhibitors, imidazole and phosphate on cyclic CMP phosphodiesterase are different from those on cyclic AMP and cyclic GMP phosphodiesterases. 8 41

A number of 3-bromo-, 3-nitro-, and 3-ethoxycarbonyl-5,7-dialkylpyrazolo[1,5-a]pyrimidines were synthesized and screened as in vitro cAMP phosphodiesterase inhibitors. The condensation of 3-aminopyrazole with symmetrical beta-diketones (acetylacetone, heptane-3,5-dione, etc.) afforded symmetrical dialkylpyrazolo[1,5-a]pyrimidines (5). The reaction of 3-aminopyrazole with unsymmetrical beta-diketones (hexane-2,4-dione, heptane-3,5-dione, etc.) gave a mixture of 5-methyl-7-alkylpyrazolo[1,5-a]pyrimidine (3) and 5-alkyl-7-methylpyrazolo[1,5-a]pyrimidines (4). The technique for the separation of 3 from 4 is described. The inhibition constants, alpha (the ratio of the molar I50 of theophylline to the molar I50 of the test compounds), were subjected to a Hansch correlation analysis. The results indicated that PDE isolated from beef heart tissue was most sensitive to changes in the length of the alkyl group in the 5 position of the pyrazolo[1,5-a]pyrimidine ring, whereas the PDE isolated from rabbit lung tissue was more sensitive to changes in the length of the 7-alkyl group. Experimentally and theoretically, the n-propyl group was found to approximate the ideal size for the alkyl group in both the 5 and 7 positions;5,7-di-n-propyl-3-ethoxycarbonylpyrazolo[1,5-a]pyrimidine (5e) was the most potent inhibitor of both lung and heart PDE.
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PMID:Adenosine cyclic 3',5',-monophosphate phosphodiesterasr inhibitors. 2.3-Substituted 5,7-dialkylpyrazolo [1,5-a]pyrimidines. 16 80

In the isolated papillary muscle of the rabbit the time course of the effects of selective beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3',5'-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3 times 10(-7) M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10(-4) M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10(-5) M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile forced and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3 times 10(-7) M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10(-4) M) was not affected by papaverine (10(-5) M). Furthermore, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by beta-adrenoceptor stimulation, and indicate further that the stimulation of alpha-adrenoceptors evokes its positive inotropic effec through a mechanism other than that elicited by beta-adrenoceptor stimulation, i.e., independent of cAMP.
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PMID:The time course of the effects of beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle. 16 86

Pentifylline (1-hexyl-3,7-dimethylxanthine equals SK 7, the main active principle in Cosaldon) inhibits the soluble and the particulate cyclic AMP phosphodiesterases (PDE I and PDE II) from bovine platelets. I50 PDE I equals 2.0 x 10(-3)M; I50 PDE II equals 8.1 x 10(-4)M. The type of inhibition of both PDE's was non-competitive.
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PMID:Inhibition of platelet cyclic 3',5'-adenosine-monophosphate phosphodiesterases by pentifylline. 17 Sep 44

The relationship between cyclic AMP-phosphodiesterase (cAMP-PDE) inhibition and inhibition of epidermal mitosis was examined for several compounds using a soluble, low Km PDE activity from hairless mouse skin and the G2 mouse ear mitosis assay. Orders of potency determined at IC50 levels (concentrations required for 50% inhibition) were SQ 20009 greater than RO 20-1724 greater than papaverine greater than bufexamac greater than indomethacin greater than theophylline greater than p-biphenylylacetic acid greater than or less than glycyrrhetinic acid for inhibition of both PDE and mitosis. The disproportionately high antimitotic potency of puromycin relative to PDE inhibition was believed to reflect effects on protein biosynthesis. Activity of the three nonsteroidal anti-inflammatory agents (bufexamac, indomethacin, and p-biphenylylacetic acid) was unrelated to their effect on prostaglandin synthesis in homogenates of hairless mouse skin. The results suggest that the epidermal antimitotic activity of the compounds tested is related to their inhibition of cAMP-PDE and provide additional support for cAMP as a regulator of the G2 stage of the epidermal cell cycle.
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PMID:Cyclic AMP-phosphodiesterase and epidermal mitosis. 18 95

The correlations between the relaxing effect of papaverine derivatives, inhibition of low Km-phosphodiesterase (cAMP-PDE = EC 3.1.4.17) activity and cyclic 3',5'-AMP (cAMP) levels in isolated rabbit ileum were investigated. There was a strong correlation between the relaxing effect, inhibition of PDE activity and cAMP content for eupaverine, ethylpapaverine and papaverine. Eupaverine was the most effective relaxing agent (I50 = 7.5 muM) and the most potent inhibitor of PDE activity (Ki = 0.6 muM), followed by ethylpapaverine (I50 = 10 muM;Ki 0.8 muM) and papaverine (I50 = 20 muM;Ki = 2 muM). In contrast, there was a strong relaxing effect (I50 = 6 muM) but only slight inhibition of PDE activity (Ki = 350 muM) by tetrahydropapaveroline (THP). The adenylate cyclase stimulating effect of THP which was shown by others is most likely the reason for comparatively higher cAMP levels, which were found to be elevated about seven times over basal levels of 0.35 nmoles/g wet weight, and effective relaxation. Relaxation could be induced by exogenously added cAMP (I50 = 45 muM) and dibutyryl-cAMP (I50 = 450 muM). Our results support the assumption that smooth muscle relaxation in rabbit ileum is mediated by cAMP. Some of these observations have been published in abstract form (Schulz and Berndt, 1972).
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PMID:Influence of papaverine derivatives on phosphodiesterase activity, cyclic 3',5'-AMP levels and relaxing effect on rabbit ileum. 18 61

Two forms of phosphodiesterase exist in the rat striatum, one with high (PDE -- I), and one with low (PDE -- II) affinity to substrate (cyclic 3',5'-AMP). The results obtained suggest that inhibition of PDE -- I activity by apomorphine or amantadine is partially related to their stimulating effect on dopaminergic system in the striatum.
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PMID:Effect of drugs stimulating dopaminergic system on phosphodiesterase activity in rat striatum. 18 92

The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(--)-delta-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.
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PMID:Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain. 19 79


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