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)

Strips of the rabbit pulmonary artery preincubated with 3H-noradrenaline were superfused with physiological salt solution containing cocaine, corticosterone and propranolol. Basal tritium efflux and electrically evoked tritium overflow were determined. The basal efflux of tritium was not affected by forskolin 0.01-10 mumol/l, 8-Br-cAMP and dibutyryl-cAMP 10-330 mumol/l, or the phosphodiesterase inhibitors rolipram 1-10 mumol/l and AH 21-132 l mumol/l; it was increased by AH 21-132 10-100 mumol/l. Forskolin concentration-dependently increased the evoked 3H overflow, and this effect was not attenuated by omission of cocaine. The facilitatory effect of forskolin was more pronounced at 0.66 Hz than at 2 Hz. Rolipram, AH 21-132, 8-Br-cAMP or dibutyryl-cAMP also produced a concentration-dependent increase in evoked 3H overflow (8-Br-cAMP was more effective than dibutyryl-cAMP in this respect). Except for the highest concentration investigated, AH 21-132 was more effective in facilitating evoked overflow than in increasing basal efflux. Forskolin, AH 21-132 or 8-Br-cAMP did not alter the percentages of 3H-noradrenaline and 3H-metabolites contained in basal tritium efflux or in stimulation-evoked tritium overflow. When a combination of AH 21-132 plus 8-Br-cAMP or AH 21-132 plus forskolin was administered, the facilitatory effect on evoked tritium overflow was more pronounced than with the single compounds alone. ACTH1-24 also facilitated the evoked tritium overflow. Combined exposure to ACTH1-24 plus forskolin, ACTH1-24 plus AH 21-132 or ACTH1-24 plus forskolin plus AH 21-132 resulted in a clearly more pronounced increase in evoked tritium overflow than exposure to the single compounds alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of cAMP for regulation of impulse-evoked noradrenaline release from the rabbit pulmonary artery and its possible relationship to presynaptic ACTH receptors. 609 33

The efficacy of the selective adenosine cyclic 3',5'-monophosphate (cAMP) phosphodiesterase (PDE) inhibitor (+/-)-rolipram and its optical isomers (0.006 to 25 mg kg-1) in inducing characteristic behavioural changes like hypothermia, hypoactivity, forepaw shaking, grooming and head twitches in rats has been examined. (+)-Rolipram was found some 15 times less potent than the racemate suggesting a stereoselective interaction with a rat brain cAMP phosphodiesterase isoenzyme. Following their intracerebral administration, the stereoisomers also demonstrated their unusual potency ratio. These findings suggested that (+)-rolipram is a less potent neurotropic PDE inhibitor in-vivo than its (-)-enantiomer.
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PMID:Neurotropic effects of the optical isomers of the selective adenosine cyclic 3',5'-monophosphate phosphodiesterase inhibitor rolipram in rats in-vivo. 613 85

The significance of a characteristic symptomatology (hypothermia, hypoactivity, forepaw shaking, grooming, head twitches) as a potential in vivo correlate of enhanced availability of brain adenosine cyclic 3',5'-monophosphate (cAMP) was examined in rats following systemic administration of various doses of dibutyryladenosine cAMP (dBcAMP) or of the phosphodiesterase (PDE) inhibitors rolipram, Ro 20-1724, ICI 63-197, isobutylmethylxanthine (IBMX) theophylline, cartazolate, and papaverine. The various PDE inhibitors could be assigned to three groups according to the pattern of behavioral alterations they induced. Rolipram, Ro 20-1724, and ICI 63-197 (group 1) caused hypothermia, hypoactivity, forepaw shaking, grooming, and head twitches. All behavioral effects were mimicked by dBcAMP but not dBcGMP. The order of potency and effective dosage range to induce the behavioral alterations were, in descending order, rolipram (0.09-1453 mumol/kg IP), ICI 63-197 (0.48-119 mumol/kg IP), Ro 20-1724 (5.6-1438 mumol/kg IP), corresponding with the recently reported efficacy of the drugs to elevate rat brain cAMP in vivo. Comparatively high doses of the alkylxanthine PDE inhibitors IBMX and theophylline (group 2) caused hypothermia, forepaw shaking, grooming, and head twitches concomitantly with a decline of the motor stimulatory effect, suggesting enhanced availability of brain cAMP. The order of potency and the effective dosage range to induce the behavioral alterations were, in descending order, IBMX (28.1-113 mumol/kg IP) and theophylline (139-555 mumol/kg IP). The third group, papaverine (295-1179 mumol/kg IP) and cartazolate (21.5-345 mumol/kg IP), caused only hypothermia and hypoactivity. The differences in the behavioral pattern of the two latter groups of compounds in comparison with dBcAMP and the selective cAMP PDE inhibitors are discussed with regard to their additional interference with adenosine actions besides their nonselective PDE inhibitory action.
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PMID:Characteristic behavioural alterations in rats induced by rolipram and other selective adenosine cyclic 3', 5'-monophosphate phosphodiesterase inhibitors. 618 75

The effect of the phosphodiesterase (PDE) inhibitors rolipram, Ro 20-1724 and isobutylmethylxanthine (IBMX) on motor behaviour and rectal temperature was studied in mice, rats and guinea pigs following intraperitoneal administration (0.39 to 25 mg/kg). The selective adenosine cyclic 3',5'-monophosphate (cAMP) PDE inhibitors rolipram and Ro 20-1724 in each species caused a dissimilar pattern of neurotropic effects: Hypothermia and hypokinesia in mice, hypothermia, hypokinesia and head twitches in rats, hypothermia, hyperkinesia and head twitches in guinea pigs. The head twitches were associated with forepaw shaking and increased grooming. Rolipram was the most potent compound in the three species. In guinea pigs it was less active than in rats or mice. Ro 20-1724 was approx. 15 to 30 times less potent in inducing the characteristic alterations in the various species. The alkylxanthine PDE inhibitor IBMX, 0.39 to 6.25 mg/kg, slightly stimulated the locomotor activity of mice and rats, most probably due to antagonism of central adenosine actions. IBMX, 6.25 to 25 mg/kg, caused a pattern of neurotropic effects identical to that produced by the selective cAMP PDE inhibitors, indicating the prevalence of the cAMP PDE inhibitory action over the adenosine antagonistic action at higher dosages. IBMX was approx. as potent as Ro 20-1724 in this respect. The species differences in the neurotropic responses to cAMP PDE inhibition in vivo presumably reflect similar differences in the extent of cAMP accumulation in brain tissue of the three species in vitro. Enhanced availability of brain cAMP in vivo in the various rodent species seems to be correlated with diverse patterns of more or less complex motor behavioural symptoms.
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PMID:Species differences in behavioural effects of rolipram and other adenosine cyclic 3H, 5H-monophosphate phosphodiesterase inhibitors. 619 Sep 91

Effects of three phosphodiesterase (PDE) inhibitors (rolipram, IBMX, and Ro 20-1724) were studied in mice in some tests predictive for antidepressant activity. All the drugs antagonized reserpine-induced hypothermia and slightly antagonized reserpine-evoked hypoactivity. Rolipram and IBMX were also effective in behavioral despair test. On the other hand, the examined PDE inhibitors did not affect apomorphine-induced hypothermia and did not potentiate the central action of L-DOPA. These results show that psychopharmacological profile of the PDE inhibitors differs from that of classical imipramine-like antidepressants.
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PMID:Antidepressant properties of some phosphodiesterase inhibitors. 619 18

A phosphodiesterase inhibitor 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (Rolipram, 10 mg/kg IP) administered immediately, but not 3 hr post-training, reversed an amnesia for an inhibitory avoidance response induced by the protein synthesis inhibitor anisomycin. Immediate post-training administration of Rolipram also enhanced retention for a weakly learned avoidance response. Unshocked animals did not show increased test latencies thus ruling out conditioned aversion as an explanation for the enhanced avoidance. Mice treated with Rolipram (10 mg/kg after training showed elevated cyclic AMP but not cyclic GMP in frontal cortex, thalamus, and hypothalamus. These results support the suggestion that cyclic AMP may play a role in memory processes.
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PMID:Brain cyclic AMP and memory in mice. 629 76

Following intraperitoneal administration, the selective cAMP phosphodiesterase (PDE) inhibitors rolipram, ICI 63 197 and Ro 20-1724 were investigated in mice in comparison with imipramine for their effectiveness in two classical test models for prediction of clinical antidepressant activity: antagonism of reserpine-induced hypothermia or hypokinesia and potentiation of yohimbine lethality. Rolipram was approximately 15 times more potent than imipramine or Ro 20-1724 and approximately as potent as ICI 63 197 in antagonizing reserpine-induced hypothermia. The antihypothermic effect of the phosphodiesterase inhibitors occurred at a smaller dose than that of imipramine. In contrast to imipramine, the phosphodiesterase inhibitors reversed reserpine-induced hypokinesia. Rolipram was approximately as potent as ICI 63 197 and about 15 times more potent than Ro 20-1724. Rolipram was approx. 5 times more potent than Ro 20-1724 and approx. as potent as imipramine or ICI 63 197 in potentiating the lethality of yohimbine. In both test models the (-)-isomer of rolipram was approx. 10-15 times more potent than the (+)-isomer, indicating a stereospecific mechanism of action. The present data suggest an antidepressant action of selective cAMP phosphodiesterase inhibitors due to enhancement of central noradrenergic transmission. The hypothesis is put forward that the increase of noradrenaline turnover induced by phosphodiesterase inhibitors in conjunction with the inhibitory action of the compounds on cAMP metabolism enables more efficient adaptative changes to occur at central synapses resulting in a rapid onset of the antidepressant activity. Preliminary results with rolipram in patients with endogenous depression seem to support this assumption.
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PMID:Potential antidepressant activity of rolipram and other selective cyclic adenosine 3',5'-monophosphate phosphodiesterase inhibitors. 630 50

The effects of Rolipram, a new phosphodiesterase inhibitor, were assessed in a double-blind trial versus placebo in 10 patients with Parkinson's disease already under treatment. Contrary to previous findings with specific phosphodiesterase inhibitors, with Rolipram (at the dose of 3 mg per day), no significant deterioration of the therapeutic action of dopamine agonist Lisuride was noted.
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PMID:Therapeutic use of a selective cAMP phosphodiesterase inhibitor (Rolipram) in Parkinson's disease. 630 87

We investigated the effects of rolipram, a selective cyclic adenosine 3',5'-monophosphate phosphodiesterase type IV inhibitor, and isobutylmethylxanthine, a nonselective phosphodiesterase inhibitor, on purposeless spontaneous chewing movements and tongue protrusions produced by 24 weeks treatment with haloperidol decanoate (25 mg/kg every 4 weeks i.m.) in rats, to examine our hypothesis that restoration of striatal cyclic adenosine 3',5'-monophosphate levels previously reduced due to dopamine D2 receptor supersensitivity, may suppress these movements. Tests were performed 8 weeks after the final injection. Haloperidol treatment significantly increased dyskinetic movements and striatal dopamine D2 receptor density compared with controls. Rolipram (0.1-1.0 mg/kg i.p.) suppressed these movements in a dose-dependent manner, whereas isobutylmethylxanthine (2 mg/kg i.p.) only slightly suppressed the syndrome and doses higher than 5 mg/kg i.p. produced other intensive movements. These results support our hypothesis and suggest that rolipram may have a therapeutic effect on tardive dyskinesia.
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PMID:Suppression of oro-facial movements by rolipram, a cAMP phosphodiesterase inhibitor, in rats chronically treated with haloperidol. 749 91

To clarify the functional significance of type IV phosphodiesterase (PDEIV) in neurons and glia cells [3H]rolipram binding and phosphodiesterase (PDE) activity were examined in cytosol and membrane fractions of neuroblastoma N18TG-2 and glioma C6Bu-1 cells. [3H]Rolipram binding was highly observed in cytosolic fractions of N18TG-2 compared to C6Bu-1. Binding was hardly observed in membrane fractions of both types of cells. Rolipram strongly (70%) inhibited the hydrolytic activity of cAMP in cytosolic fractions of N18TG-2. The activity in cytosol fractions of C6Bu-1 was slightly (20%) inhibited by rolipram. These results suggest that PDEIV plays important roles in neurons.
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PMID:[3H]Rolipram binding and phosphodiesterase activity in neuroblastoma N18TG-2 and glioma C6Bu-1. 752 96


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