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)

In order to characterize age differences in the lipolytic effect of catecholamines on tests of subcutaneous adipose tissue of test persons aged from 0.1 to 10 years, from 20 to 40 years, and from 60 to 75 years the influence of propranolol, phentolamine and theophyllin on the release of glycerol by isoprenalin and adrenalin was investigated. Propranolol (10(8) and 10(5) mol/1) inhibits the lipolysis in the adipose tissue of all age groups stimulated by isoprenalin (10(6)and 10(5) mol/1). The following Ki-values were calculated: 2x10(6) mol/1in the tissue of adults, 0.5 x 10(6) mol/1 in the infantile adipose tissue, 0.2 X 10(6) mol/1 in the tissue of old persons. Phentolamine (10(5) mol/1) increases the lipolytic effect of adrenalin (10(5) mol/1), there are no age differences. Theophyllin (10 (2) mol/1) increases the release of glycerol induced by isoprenalin (10(5) mol/1) in infantile and adult adipose tissue, however, it has no influence on them in the adipose tissue of old man. The findings suggest the higher sensitivity of the fat cells of the ageing organism to beta-adrenergics underlies a higher affinity of the adrenergics to the specific beta-adrenoceptors in the cytoplasm membrane of the adipocytes. The more intensive lipid mobilization in old age by beta-adrenergics is explained by a low activity of the cAMP-phosphodiesterase of the fat cells and by the higher and possibly longer lasting increase of intracellular cAMP in this age group.
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PMID:[Age-dependence of catecholamine effects in man. IV. Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics]. 1 47

Imidazole (0.73-15.9mM) was found to increase both tension developed Td and the maximum rats of rise of tension, dT/dtmax, in the isolated hemidiaphragm of the rat during indirect stimulation. Similar effects were obtained during direct stimulation and in the presence of d-tubocurarine. Imidazole (0.73-22 mM) antagonized the action of d-tubocurarine. This effect was particularly pronounced in preparations pretreated with imidazole. Propranolol did not significantly change the action of imidazole on Td and dT/dtmax during direct stimulation. Similarly, propranolol did not affect the action of low concentrations of imidazole during indirect stimulation. When present in the bath for periods of time longer than 15 min, propranolol significantly depressed the effect of even high concentrations of imidazole on Td and dT/dtmax during indirect stimulation. Histamine (0.18-0.91 mM) did not affect either Td or dT/dtmax. In the experiments in vivo, imidazole (12.5-100 mg/kg) produced a small increase both in Td and dT/dtmax of the gastrocnemius muscle during sciatic nerve stimulation. The available evidence indicates that the action of imidazole on Td and dT/dtmax is not connected with its action on phosphodiesterase, but it is most probably due to a direct action on the muscle.
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PMID:The effect of imidazole on the isometric contractility of the isolated hemidiaphragm of the rat. 17 19

In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or calcium chloride (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of adenosine 3',5'-cyclic phosphate (cAMP). Prolonged prostaglandin E2 (pge2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+ were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. It is suggested that PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents.
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PMID:Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity. 17 82

Bile acids cause diarrhea by inducing colonic secretion, probably mediated through the cyclic AMP system. The aim was to determine the effects of an adenylate cyclase inhibitor, propranolol, on deoxycholic acid (DCA) stimulation of net secretion and the cyclic AMP system in the colon. In each of 30 New Zealand white rabbits, 0.9% NaC1 as control and 6 mM and 8 mM DCA were injected in random sequence into three colonic loops in situ. Propranolol, 4 mg per kg was administered intravenously to 12 of the 30 rabbits 1/2 hr before preparation of the loops, i.e., 5 1/2 hr before the rabbits were killed. In the 18 untreated animals, 6 and 8 mM DCA significantly stimulated colonic net secretion and mucosal adenylate cyclase activity; 6 mM DCA caused no change in mucosal phosphodiesterase activity, whereas 8 mM DCA caused a 25% decrease (P less than 0.01). In propranolol-treated animals compared to untreated animals, the volume of luminal fluid in controls was not different, with 6 mM DCA it was 88% less (P less than 0.01), and with 8 mM DCA it was 45% less (P less than 0.01); adenylate cyclase activity in controls was 43% less (P less than 0.01), with 6 mM DCA it was 67% less (P less than 0.01), and with 8 mM DCA it was 65% less (P less than 0.01); phosphodiesterase activity in controls and with 6 mM DCA was not different and with 8 mM DCA it was 38% greater (P less than 0.02). In conclusion, propranolol prevented DCA stimulation of colonic net secretion and inhibited the cyclic AMP system. Propranolol, therefore, warrants investigation as therapy for diarrhea caused by bile acids in the colon.
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PMID:Propranolol inhibits adenylate cyclase and secretion stimulated by deoxycholic acid in the rabbit colon. 17 10

In liver cells isolated from fed female rats, glucagon (290nM) increased adenosine 3':5'-monophosphate (cyclic AMP) content and decreased cyclic AMP binding 30 s after addition of hormones. Both returned to control values after 10 min. Glucagon also stimulated cyclic AMP-independent protein kinase activity at 30 s and decreased protein kinase activity assayed in the presence of 2 muM cyclic AMP at 1 min. Glucagon increased the levels of glycogen phosphorylase a, but there was no change in total glycogen phosphorylase activity. Glucagon increased glycogen phosphorylase a at concentrations considerably less than those required to affect cyclic AMP and protein kinase. The phosphodiesterase inhibitor, 1-methyl-3-isobutyl xanthine, potentiated the action of glucagon on all variables, but did not increase the maximuM activation of glycogen phosphorylase. Epinephrine (1muM) decreased cyclic AMP binding and increased glycogen phosphorylase a after a 1-min incubation with cells. Although 0.1 muM epinephrine stimulated phosphorylase a, a concentration of 10 muM was required to increase protein kinase activity. 1-Methyl-3-isobutyl xanthine (0.1 mM) potentiated the action of epinephrine on cyclic AMP and protein kinase. (-)-Propranolol (10muM) completely abolished the changes in cyclic AMP binding and protein kinase due to epinephrine (1muM) in the presence of 0.1mM 1-methyl-3-isobutyl xanthine, yet inhibited the increase in phosphorylase a by only 14 per cent. Phenylephrine (0.1muM) increased glycogen phosphorylase a, although concentrations as great as 10 muM failed to affect cyclic AMP binding or protein kinase in the absence of phosphodiesterase inhibitor. Isoproterenol (0.1muM) stimulated phosphorylase and decreased cyclic AMP binding, but only a concentration of 10muM increased protein kinase. 1-Methyl-3-isobutyl xanthine potentiated the action of isoproterenol on cyclic AMP binding and protein kinase, and propranolol reduced the augmentation of glucose release and glycogen phosphorylase activity due to isoproterenol. These data indicate that both alpha- and beta-adrenergic agents are capable of stimulating glycogenolysis and glycogen phosphorylase a in isolated rat liver cells. Low concentrations of glucagon and beta-adrenergic agonists stimulate glycogen phosphorylase without any detectable increase in cyclic AMP or protein kinase activity. The effects of alpha-adrenergic agents appear to be completely independent of changes in cyclic AMP protein kinase activity.
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PMID:Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines. 18 18

Acute administration of morphine sulfate at 20 mg/kg decreased mouse cerebellar adenosine 3',5'-cyclic phosphate (cAMP) levels while not affecting cAMP phosphodiesterase (EC 3.1.4.17). The cAMP levels and cAMP phosphodiesterase activies were not affected by chronic treatment. However, cAMP levels increased during abrupt withdrawal both with and without naloxone precipitation, with cAMP phosphodiesterase activities being correspondingly decreased. Propanolol prevented the cAMP increase during abrupt withdrawal.
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PMID:Cerebellar cAMP levels following acute and chronic morphine administration. 19 Nov 70

1. Cold storage treatment of the guinea-pig taenia caecum had a greater inhibitory effect on the isoprenaline-induced relaxation than that induced by phenylephrine. Prolonged cold storage (12-14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3',5'-monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage. 2. After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose-dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold-stored preparations. 3. In the fresh preparation, the onset of the isoprenaline (10(-6)M)-induced relaxation preceded the increase in tissue cyclic AMP. 4. Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level. 5. Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP. 6. The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage. 7. Propranolol inhibited both the isoprenaline-induced relazation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events. 8. Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of beta-adrenoceptors but are independent phenomena.
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PMID:Effect of isoprenaline and phenylephrine on the adenosine 3',5'-monophosphate content and mechanical activity of cold-stored and fresh taenia caecum from the guinea-pig. 19 53

Dispersed pinealocytes have been used to study the role of adenosine 3',5'-monophosphate (cyclic AMP) in the "turnoff" of N-acetyltransferace activity. Activity was first stimulated 100-fold by treating cells with 1-norepinephrine. 1-Propranolol acted stereospecifically to rapidly reverse this, resulting in a 70 percent loss of enzyme activity within 15 minutes. An even more rapid 1-propranolol-induced decreased in cyclic AMP also occurred. This together with the observation that the inhibitory effect of 1-propranolol on N-acetyltransferase was blocked by dibutyryl cyclic AMP and phosphodiesterase inhibitors indicate that an abrupt decrease in cyclic AMP may be the signal for the rapid decrease in pineal N-acetyltransferase activity.
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PMID:Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for "turnoff". 20 27

Pimobendan (UD-CG 115 BS), an inotropic agent and inhibitor of type III phosphodiesterase activity, is demethylated in vivo to form UD-CG 212 Cl, which is a more potent type III phosphodiesterase inhibitor. This study examined cyclic AMP (cAMP)-mediated actions of UD-CG 212 Cl. In guinea pig papillary muscles, UD-CG 212 Cl increased cAMP and stimulated Ca(++)-dependent slow action potentials (APs) in a dose-dependent manner. When compared to previous studies using pimobendan, UD-CG 212 Cl was approximately 100-fold more potent. UD-CG 212 Cl had no additional effects on slow APs in the presence of a maximal dose of isoproterenol (1 microM). Propranolol had little effect on UD-CG 212 Cl-induced slow APs. These results, along with previous studies, indicate that slow AP induction by UD-CG 212 Cl was cAMP-dependent, and the increase in cAMP levels was most likely due to phosphodiesterase inhibition and not beta receptor stimulation. Experiments with tetraethylammonium.Cl suggested that UD-CG 212 Cl probably did not induce slow APs by blocking K+ channels. In voltage-clamped ventricular myocytes UD-CG 212 Cl (100 microM) could stimulate Ca++ current (+21 +/- 5%) when basal cAMP levels were enhanced with a submaximal dose of isoproterenol (10(-9)-10(-8) M). Isoproterenol was not required to observe the stimulating effect of UD-CG 212 Cl on Ca++ current in intact, nondialyzed cells prepared using the nystatin-perforated patch method. Studies with the stereoisomers of UD-CG 212 Cl showed that the D-isomer was more potent than the L-isomer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrophysiological actions of the pimobendan metabolite, UD-CG 212 Cl, in guinea pig myocardium. 134 67

The possible role of cyclic AMP (cAMP) on tritium overflow evoked by stimulation of the cardio-accelerant nerves was studied in rat atria preincubated with [3H]-noradrenaline. Addition of the activator of adenylate cyclase forskolin (1 mumol/l), or of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 100 mumol/l), did not affect both basal and evoked overflow. However, in the presence of the alpha 2-adrenoceptor antagonist yohimbine (0.03 mumol/l) both forskolin and IBMX increased the stimulation-induced transmitter overflow by 49% and 141%, respectively (compared to yohimbine 0.03 mumol/l). Thus, in rat atria the cAMP-dependent facilitation of noradrenaline release is only present when the autoinhibition exerted by activation of prejunctional alpha 2-adrenoceptors is blocked. Propranolol (0.1 mumol/l) that did not produce any effect on noradrenaline release markedly reduced the facilitatory response induced by forskolin in the presence of yohimbine. When rats were pretreated with the beta 2-adrenoceptor agonist clenbuterol (0.3 mg.kg-1, s.c., twice daily, 14 days), a treatment which desensitizes beta-adrenoceptor-mediated facilitation of noradrenaline release (Kazanietz and Enero 1989), the facilitatory effect of forskolin and IBMX in the presence of yohimbine was abolished. The results indicate that in rat atria the effect of forskolin and IBMX on noradrenaline release are only to be observed after blockade of presynaptic alpha 2-adrenoceptor autoinhibition. beta-adrenoceptor blockade or clenbuterol pretreatment decreases the facilitatory response to forskolin and hence prejunctional beta-adrenoceptor-mediated enhancement of noradrenaline release is linked to the stimulation of adenylate cyclase.
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PMID:Role of cyclic AMP in the release of noradrenaline from isolated rat atria. Effect of pretreatment with clenbuterol. 138 33


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