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 effect of five phosphodiesterase (PDE) inhibitors (papaverine, IBMX, theophyllamine, dipyridamol and M & B 22,948) was studied on adenylate cyclase and on cyclic nucleotide phosphodiesterase activities in extracts of rat caudate nucleus. For comparison the effect on DA turnover and on turning behaviour in rats with unilateral lesions of the nigro-neostriatal DA nerurons was studied. Cyclic AMP PDE was inhibited by papaverine, dipyridamol, IBMX, M & B 22,948 and theophyllamine in that order of potency. Cylcic GMP PDE was inhibited by IBMX, papaverine, M & B 22,948 and theophyllamine, but not by dipyridamol. Basal adenylate cyclase washigher if assayed in the presence of papaverine or dipyridamol than if theophyllamine or IBMX was present. The degree of stimulation caused by DA was not significantly influenced by the PDE inhibitors. Papaverine and dipyridamol enhanced DA disappearance in the caudate nucleus and the tuberculum accumbens, but not in the median eminence. Caffeine had no significant effect. Papaverine (1-28 mg/kg) had no signigicant effect on L-dopa (5 mg/kg)-induced turning, and actually inhibited turning induced by the combination of L-dopa (10 mg/kg) and atropine (5 mg/kg). The other four PDE inhibitors all potentiated L-dopa-induced turning. Theophyllamine (20 mg/kg) and IBMX (5 mg/kg) even caused turning when given alone. The data are compatible with the opinion that PDE inhibition leads to an enhanced effect of DA in the caudate nucleus. However, the results also demonstrate that several of the PDE inhibitors have effects on central DA mechanisms that are difficult to explain solely on the basis of PED inhibition.
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PMID:Effect of some phosphodiesterase inhibitors on central dopamine mechanisms. 18 7

The time course of changes of the level of 3',5'-cyclic AMP (cAMP) and of the tension developed under stimulation of alpha- and beta-adrenoceptors by phenylephrine was investigated in the isolated rabbit papillary muscle. Furthermore the dose-response relationships for increases of cAMP and of developed tension elicited by phenylephrine were determined. 1. A submaximally effective concentration of phenylephrine (10(-5) M) increased significantly the level of cAMP of the papillary muscle at 15 and 30 s by 45 and 36% respectively; the level of cAMP returned to the control value at 60 s after the administration. The developed tension increased significantly not before 45 s and reached its maximal level at 180 s. 2. When alpha-adrenoceptors were blocked by phentolamine (10(-6) M), the positive inotropic effect of phenylephrine was decreased significantly but the increase of cAMP induced by phenylephrine was not reduced. In the presence of phentolamine the increase of cAMP induced by phenylephrine lasted longer than in the control experiments. 3. The effects of phenylephrine (10(-5) M) both on the level of cAMP and the developed tension mediated via stimulation of beta-adrenoceptors in the presence of phentolamine were enhanced by the phosphodiesterase inhibitor papaverine throughout the course of responses. 4. Phenylephrine produced an increase in developed tension as well as in cAMP. The corresponding dose-response curves run parallel to each other but differed by about 1.5 log units whereby the developed tension was evoked by lower concentrations. Phentolamine (10(-6) M) shifted the curve for the positive inotropic action by about 1.5 log units but did not affect that for increase in cAMP. Therefore, in the presence of the alpha-adrenolytic drug phentolamine the difference between both curves became smaller so that both curves were superimposed. Papaverine (10(-5) M) shifted the whole curve for cAMP upwards and enhanced the maximal contractile response to phenylephrine mediated by stimulation of beta-adrenoceptors. 5. The present results indicate that the positive inotropic action of phenylephrine in lower concentrations (less than 10(-5) M) induced by stimulation of alpha-adrenoceptors is independent of the level of cAMP. The positive inotropic action of the higher concentrations of phenylephrine induced via stimulation of beta-adrenoceptors was preceded by an accumulation of cAMP; the inhibition of the cAMP phosphodiesterase activity by papaverine enhanced the actions of phenylephrine both on the level of cAMP and on the contractile force.
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PMID:Relationship between the level of cAMP and the contractile force under stimulation of alpha- and beta-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle. 18 21

On guinea-pig heart we investigated whether cyclic AMP serves as a messenger for H1 - and/or H2-mediated responses to histamine. (1) On papillary muscle histamine elicited positive inotropic responses which were antagonized by burimamide but not by promethazine. The stimulation of H2-receptors was not only associated with an increase in contractility but also with an increase in cAMP. As shown by the time course of effects for 10(-5) M histamine, the maximal increase in cAMP preceded the maximum in contractility. The mechanical and biochemical responses to histamine were potentiated by the phosphodiesterase inhibitor papaverine, but antagonized by burimamide. (2) On the left guinea-pig atrium containing H1-receptors the inotropic response to histamine (10(-5) M) was not accompanied by increases in cAMP at stimulation frequencies of 0.5 and 2 Hz, respectively. In addition, in the presence of papaverine (3 X 10 (-5) M) no change in the cyclic AMP level occurred after application of histamine. Papaverine by itself, however, concomitantly increased contractility and cyclic AMP at a stimulation frequency of 0.5 Hz. In contrast, at 2 Hz papaverine increased only cAMP leaving the contractility unchanged. At this frequency the well-known Ca2+-antagonistic effect comes into prominence, thus masking the positive inotropic effect attributable to the inhibition of the phosphodiesterase. (3) On the right guinea-pig atrium the mediation of the positive chronotropic response to histamine by H2-receptors which is partly involved in the inotropic effect via the frequency-force relationship does not lead to a concomitant increase in cAMP. Also, in the presence of papaverine, histamine had no influence on the cAMP. However, papaverine potentiated the cardioacceleration produced by histamine. Although it is very likely that the cAMP in the sinus node rises, we were not able to detect an increase in cAMP in the whole atrial tissue. From the present results the conclusion can be drawn that the mediation of the inotropic effect due to stimulation of H2-receptors by histamine is associated with an increase of cyclic AMP, whereas that of H1-receptors is not. The view that cAMP may be the second messenger in the chronotropic action of histamine needs further elucidation by experiments on sino-atrial cells.
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PMID:H1 - and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts. 19 83

Papaverine enhances the spontaneous release of 3H-dopamine from rat brain striatal synaptosomes and 3H-noradrenaline from cortical synaptosomes in a dose-dependent way. Neither dibutyryl cyclic AMP nor theophylline had any significant effect on either spontaneous or on potassium-evoked 3H-catecholamine release. It is suggested that the effect of papaverine on catecholamine release is not due to its phosphodiesterase inhibitory potency.
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PMID:The effects of dibutyryl cyclic AMP, theophylline and papaverine on the release of 3H-catecholamines from rat brain striatal and cortical synaptosomes. 20 72

Effects were examined of atropine, diazepam, pethidene, promethazine, scopolamine, omnopon and papaverine on basal and noradrenaline-stimulated lipolysis in rat isolated fat cells and on rat adipose tissue cyclic AMP phosphodiesterase activity. Papaverine at high concentration (1 mM) inhibited both basal and hormone-stimulated lipolysis, whereas diazepam enhanced basal lipolysis. At a 'clinical dose', omnopon increased both basal and noradrenaline-stimulated lipolysis. Adipose tissue cAMP phosphodiesterase activity was strongly inhibited by 1 mM diazepam, papaverine, promethazine and omnopon (280 microgram ml-1). Lack of enhancement of lipolysis by the established cAMP phosphodiesterase antagonist papaverine, is compatible with simultaneous inhibition also of adipose adenyl cyclase. Diazepam-stimulated lipolysis is compatible with its phosphodiesterase inhibitory activity. It is proposed that papaverine-containing omnopon may offer some survival advantages during surgical stress by facilitating a caloric supply.
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PMID:Effects of several preoperative medications on fat cell lipolysis, and activity of adipose tissue cyclic AMP phosphodiesterase. 22 65

Prostaglandins (PGs) are synthesised by gastric mucosa, and have been shown to inhibit gastric acid secretion and ulcer formation in man and experimental animals. Recently exogenous PGs, mainly of the E group, have been used for the treatment of peptic ulcer disease. We therefore searched for a drug that would stimulate endogenous gastric prostaglandin E(2) (PGE(2)) synthesis. Rabbit gastric mucosa slices were cultured for 22 hours at 77 degrees C. PGE(2), measured by radioimmunoassay, was found to be linearly secreted into the culture medium. PGE(2) accumulation in the medium during 22 hours of culture was 7.9+/-0.5 (SE) ng/mg tissue (N=20). Addition of papaverine (100 mu/ml), a cyclic nucleotide phosphodiesterase inhibitor, resulted in a significant increase (250% of control) in PGE(2) accumulation in the medium: 24.3+/-1.8 ng/mg tissue (N=25). Isobutylmethylxanthine (IBMX 100 mug/ml), another phosphodiesterase inhibitor, only slightly increased PGE(2) accumulation, while 8 bromo-cyclic AMP (1 mM) had no effect. Under these conditions IBMX increased by 20-fold mucosal cyclic AMP levels: 3.9+/-0.3 pmol/mg tissue (N=8) as compared with control levels: 0.2+/-0.03 pmol/mg tissue (N=8). Papaverine, however, did not alter mucosal cyclic AMP accumulation. These results indicate that papaverine stimulates PGE(2) production by cultured rabbit gastric mucosa and that this stimulation is not related to the inhibition of phosphodiesterase activity and accumulation of mucosal cyclic AMP. Papaverine induced stimulation of PGE(2) production should be further evaluated regarding its possible beneficial effects in protecting gastric mucosa and in reducing acid secretion in peptic ulcer patients.
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PMID:Papaverine stimulation of prostaglandin E2 production by cultured rabbit gastric mucosa. 23 Jan 30

Papaverine and theophylline both increase the chronotropic response of isolated rabbit atria, however, the maximum stimulation following papaverine is much smaller than that obtained with theophylline. When these phosphodiesterase inhibitors are used in conjunction with histamine (H1 and H2 receptor agonist), 2-(2-aminoethyl) pyrazole (H2 agonist) and 3-(2-aminoethyl) triazole (H1 agonist) the responses are all considerably more than additive. This suggests that both H1 and H2 histamine receptors can activate adenyl cyclase and therefore increase the formation of cyclic AMP in spite of reports that only H2 receptors stimulate adenyl cyclase.
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PMID:A comparison of the augmentation of H1 and H2 receptor agonist stimulation of rabbit atrial chronotropic response by two phosphodiesterase inhibitors, papaverine and theophylline. 69 24

The author carried out studies on male white rats and examined the effect of imidazol, papaverine and theophyline (drugs affecting the activity of phosphodiesterase), singly or in correlation with GAMA and diazepam on picrotoxic seizure threshold (PSAT). He found that imidazol had various effects on PSAT in accordance with the interval of application and antagonized the effects of GAMA. Papaverine in low doses was ineffective, but in higher doses lowered PSAT; it antagonized the effect of GAMA, elevating the threshold. Papaverine in combination with CAMF antagonized the effect of GAMA, elevating the threshold. Theophyline lowered PSAT; it did not influence the effects of the combined application of GAMA and DIA. He thinks that the obtained changes in PSAT could partly be connected with the mediating influence of imidazol, papaverine and phe theophyline on cerebral phosphodiesterase both after their single application and after examination of their correlations with GAMA or DIA, used singly or in comibination, and partly with their own pharmacologic action.
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PMID:[Effects of imidazole, papaverine and theophylline on the picrotoxin convulsion-seizure threshold. The correlation with gamma-aminobutyric acid (GABA) and diazepam]. 69 66

The effect of papaverine on renal function and renin release was investigated in dogs in vivo and in vitro. Intrarenal arterial infusion of 0.1 mg/kg/min of papaverine for 10 minutes caused a significant rise in renal blood flow, a significant decrease in renal vascular resistance, clearance and extraction ratio of creatinine and PAH and in the amount of filtered sodium, without altering arterial blood pressure. There was a significant increase in sodium excretion and in the excreted percentage of filtered sodium (TRFNa). Renin activity (PRA) of arterial blood and renal venous blood, veno-arterious PRA-difference and renin secretion increased significantly after papaverine infusion. In order to eliminate the effect of hemodynamic changes on renin secretion, the effect of papaverine (10(-5), 10(-4)M) was investigated in vitro in surviving canine kidney cortex slices. Papaverine caused a significant increase in renin release and in tissue cAMP concentration. This supports the assumption that the increase in renin secretion might be due to a direct effect on the juxtaglomerular apparatus, by blocking phosphodiesterase activity and by increasing the renal cAMP level.
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PMID:Effect of papaverine on renin release in dogs in vivo and in vitro. 75 46

The effect of papaverine on the positive inotropic response to isopreqaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose-response curve for isoprenaline was shifted to the left by papaverine (3 times 10- minus 6 to 3 times 10- minus 5 M), in a dose-dependent manner, while that for calcium was not affected by the same concentration. In this respect papaverine was about 30 times more potent than theophylline. In the presence of papaverine isoprenaline induced arrhythmic contractions of the papillary muscle: the incidence of arrhythmic contractions was positively correlated to the concentration of papaverine. Papaverine 10- minus 5 to 10- minus 4 M caused only a positive inotropic response whereas 3 times 10- minus 4 to 10- minus 3 M induced a biphasic response, i.e., after a positive inotropic effect followed a negative one. In the presence of 3 times 10- minus 4 M papaverine isoprenaline failed to cause a positive inotropic response but exclusively induced arrhythmic contractions. Calcium, on the other hand, readily antagonized the negative inotropic effect of papaverine (3 times 10- minus 4 M) and caused a contracture of the papillary muscle. The results indicate that papaverine (3 times 10- minus 6 to 10- minus 5 M) like theophylline (10- minus 4 to 10- minus 3 M) produces its effect by phosphodiesterase inhibition and thereby specifically potentiates the response through beta-adrenoceptor stimulation. In higher concentrations (3 times 10- minus 4 to 10- minus 3 M) it acts as a calcium antagonistic, like D600, and furthermore may interact with calcium moving through myocardial cell membranes to cause a contracture via a mechanism which it shares with theophylline.
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PMID:Effects of papaverine on isolated rabbit papillary muscle. 112 60


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