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)

1. Cyclic AMP and cyclic GMP levels were determined in bovine splenic nerve segments in the absence and presence of (+/-)-isoprenaline, (-)-phenylephrine, clonidine and ICI 63 197 (a phosphodiesterase inhibitor). The chosen concentrations of adrenoceptor agonists were those which are known to affect stimulation-induced overflow of noradrenaline from nerve terminals. 2. The mean levels of cyclic AMP ranged from 229 to 555 pmol/g of microwave irradiated tissue. Mean cyclic GMP levels ranged from 27.9 to 42.2 pmol/g. 3. Isoprenaline enhanced cyclic AMP levels but did not affect cyclic GMP levels. The effect was blocked with (+/-)-propranolol. ICI 63 197 increased cyclic AMP levels but did not change cyclic GMP. Phenylephrine and clonidine caused no consistent changes in cyclic AMP or cyclic GMP levels or in the concentration ratio between these two nucleotides. 4. The results support the involvement of cyclic AMP in the enhancing effect of beta-adrenoceptor agonists and phosphodiesterase inhibitors on stimulation-induced release of noradrenaline from sympathetic nerves.
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PMID:Effects of alpha- and beta-adrenoceptor agonists and a phosphodiesterase inhibitor (ICI 63 197) on cyclic AMP and GMP levels in bovine splenic nerve. 613 92

Primary culture of bovine adrenal subcapsular cells was used to investigate direct effects of catecholamines on aldosterone secretion. Cells dispersed with collagenase and DNAse and cultured at high density (1.5-2 million/ml) for 3 days displayed high sensitivity to angiotensin II and ACTH, with an ED50 of 1.4 and 1.5 nM, respectively. Adrenergic agonists elicited a 4- to 6-fold stimulation of aldosterone secretion with potency order (-)isoproterenol greater than (-)epinephrine equals (-)norepinephrine greater than (+)isoproterenol, and corresponding ED50 5, 240, 213, and 3000 nM, respectively. No reproducible inhibition by dopamine of basal or stimulated levels of aldosterone secretion could be detected, but a weak stimulatory effect was sometimes observed at high concentration greater than 10 microM. (-)Isoproterenol stimulation of aldosterone production was potently inhibited by the beta-adrenergic antagonists (-)alprenolol and (+)alprenolol with potencies of 1.8 and 110 nM, respectively. The alpha-adrenergic antagonists prazosin, yohimbine, and phentolamine only weakly inhibited (-)isoproterenol stimulation with potencies of 5, 13, and 140 microM, respectively. The potent beta 2-adrenergic antagonist ICI 118.551 and the weaker beta 1-adrenergic antagonist atenolol were roughly equipotent with potencies of 0.27 and 0.44 microM, respectively. Addition of the phosphodiesterase inhibitor Ro 20-1724 at 10 microM doubled the maximum stimulation effect of (-)isoproterenol without changing the potency of the catecholamine or the basal level of aldosterone secretion, suggesting a potential role of cAMP as a mediator of isoproterenol stimulation. These results indicate the presence of a beta 1-adrenergic receptor stimulating aldosterone secretion in bovine zona glomerulosa cells. The physiological significance of direct beta-adrenergic stimulation of aldosterone production is currently being assessed.
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PMID:Direct beta-adrenergic stimulation of aldosterone secretion in cultured bovine adrenal subcapsular cells. 614 9

The role of the presynaptic alpha and beta-adrenoceptors on the regulation of tyrosine hydroxylase activity was studied in guinea pig atria depolarized with 50 mM K+. The presence of the beta-blocker propranolol (0.1 microM), alpha-blockers phentolamine (0.31 microM) or yohimbine (0.3 microM) or the alpha-agonist clonidine (0.1 microM) in the incubation medium did not affect tyrosine hydroxylase activation by 50 mM K+. On the contrary, the beta-agonist isoproterenol (0.012 microM) potentiated the activation produced by 50 mM K+, effect blocked by propranolol. Also the phosphodiesterase inhibitor, 1-methyl-3-isobutyl-xanthine (100 microM), facilitated tyrosine hydroxylase activation by potassium. Isoproterenol might exert its facilitatory effect through the stimulation of presynaptic beta-adrenoceptors, activation of adenyl cyclase and consequent increase of the intraneuronal concentration of cAMP. Noradrenaline synthesis in guinea pig atria depolarized by K+ seems to be unrelated to the stimulation of presynaptic adrenoceptors and also independent of the regulation of neurotransmitter release.
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PMID:Presynaptic adrenoceptors on the regulation of tyrosine hydroxylase activation by potassium. 615 72

Basophil-rich rabbit leucocytes sensitized by anti-horseradish peroxidase antibodies released platelet-activating factor (PAF) and histamine upon exposure to the specific antigen. This release was preceded and accompanied by a sharp decrease in the intracellular concentration of cyclic AMP. Isoproterenol, a beta-adrenergic agent, and theophylline, a phosphodiesterase inhibitor, used individually or in combination, increased the intracellular concentration of cyclic AMP and inhibited the release of both PAF and histamine. Propranolol, a beta-adrenergic blocking agent, suppressed the effect of isoproterenol on cyclic AMP level and mediator release. Dibutyryl cyclic AMP, an alkylated derivative of cyclic AMP, inhibited PAF and histamine release. These results indicate that cyclic AMP, which is known to control the release of other mediators of immediate hypersensitivity, also regulates the release of PAF. Histamine and PAF followed one another closely in all of our release or inhibition experiments, bringing more evidence for the basophil origin of PAF.
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PMID:Pharmacological modulation of platelet-activating factor (PAF) release from rabbit leucocytes. I. Role of cAMP. 615 8

Divalent cations and agents elevating cellular cAMP were tested for their effects on parathyroid hormone (PTH) secretion and protein kinase activity in dispersed bovine parathyroid cells. After incubation with secretagogue for 5-30 min, cells were sedimented, PTH in the supernatant was determined by RIA, and the pellet was disrupted by sonication for the measurement of protein kinase activity. Preliminary studies established conditions where the protein kinase activity ratio (AR = activity in the absence divided by that in the presence of 10(-6) M cAMP in the kinase assay) remained stable during the preparation and assay of cellular extracts. (-)Isoproterenol caused a rapid (within 5 min) increase in the AR from 0.28 to 0.63, which returned to 0.25-0.3 within 5 min after the addition of the potent beta-adrenergic blocker (-)propranolol. (-)Isoproterenol, dopamine, and the phosphodiesterase inhibitor methylisobutylxanthine caused parallel, dose-dependent increases in PTH release and the protein kinase AR of 2- to 2.5-fold. Calcium and magnesium, on the other hand, despite causing 2- to 4-fold inhibition of secretion at 2 and 5 mM, respectively, had no effect on the AR. Calcium (2.0 mM) likewise had only a modest (0-25%) inhibitory effect on the isoproterenol-stimulated increase in the AR in spite of a 3- to 4-fold inhibition of agonist-stimulated secretion. These results suggest that the stimulation of secretion associated with agents that elevate cAMP is mediated by cAMP. Changes in the degree of activation of protein kinase, on the other hand, cannot quantitatively for the effects of divalent cations on basal or agonist-stimulated secretion.
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PMID:Adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase and the regulation of parathyroid hormone release by divalent cations and agents elevating cellular cAMP in dispersed bovine parathyroid cells. 617 21

The effects of the beta-adrenergic hormone agonist, isoproterenol, on testosterone and cyclic AMP production in mouse Leydig cells in culture have been investigated. It was found that isoproterenol increased testosterone production on days 1, 2 and 3 of culture but not in freshly cultured cells. Cyclic AMP production was however increased on all days of culture. In subsequent studies carried out on day 2 of culture the amounts of testosterone formed during incubation with isoproterenol were 20-90% of those obtained with maximum stimulating levels of luteinizing hormone. The amounts of cyclic AMP formed were extremely low compared with those obtained with luteinizing hormone (22 +/- 5.3 and 2320 +/- 100 pmoles/10(6) cells/2 h respectively). Isoproterenol (10(-8) -10(-7) M) gave a significant increase in testosterone production and reached a maximum with 10(-6) M. Similar dose-response curves for cyclic AMP production were obtained. The stimulation of cyclic AMP and testosterone by isoproterenol was highly dependent on the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. Propranolol blocked, in a dose-dependent manner, both isoproterenol-stimulated cyclic AMP and testosterone production. In the presence of excess luteinizing hormone no additional effects of isoproterenol were detected. Epinephrine also stimulated testosterone production. It is concluded that catecholamines stimulate testosterone production in mouse Leydig cells in monolayer culture and that this effect if mediated by cyclic AMP.
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PMID:Catecholamine stimulation of testosterone production via cyclic AMP in mouse Leydig cells in monolayer culture. 618 Sep 42

The mesangial cell is a glomerular cell type with smooth muscle-like (contractile) properties. The responses evoked in cultured mesangial cells by catecholamines were examined in the presence or absence of prostaglandin E2 (PGE2) with or without a phosphodiesterase inhibitor. Exposure to 10(-4) M norepinephrine, epinephrine, or isoproterenol elevated intracellular cyclic AMP (cAMP) levels in mesangial cells (25th to 30th passages) nearly threefold. If isobutylmethylxanthine (MIX) was also included, the hormones caused marked further increases in cAMP (after a 20-min incubation, control with MIX, 64.2 +/- 5.2 pmoles/mg protein; 10(-4) M norepinephrine, 4266 +/- 284 pmoles/mg protein; 10(-4) M epinephrine, 5812 +/- 173 pmoles/mg protein; and 10(-4) M isoproterenol, 3136 +/- 114 pmoles/mg protein). Under both of these circumstances (that is, catecholamines with or without MIX) greater than 50% of the cells underwent a change in shape (that is, had a round cell body with long, thin tapered processes). The cAMP and shape change response was independent of extracellular calcium ions and appeared to be due to beta-adrenergic stimulation. Isoproterenol with MIX stimulated an alteration in morphology and cAMP production at concentrations of 10(-4) M to 10(-9) M. Within 10 min following beta-adrenergic stimulation (10(-4) M isoproterenol plus MIX) cAMP was maximum; at this time a shape change was first evident. Eighty-five to one hundred percent of the cells had undergone a shape change by 40 min. Dibutyryl cAMP (10(-3) M) also induced a shape change in cultured mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP-associated shape change in mesangial cells and its reversal by prostaglandin E2. 620 73

Isoprenaline, but not prenalterol, produced positive inotropy in guinea-pig papillary muscle. Prenalterol was a competitive antagonist of responses to isoprenaline in this tissue with a pKB of 7.24, as estimated by a Schild regression. Guinea-pig papillary muscles pretreated with the phosphodiesterase inhibitor, isobutylmethylxanthine (IMX), were 10 times more sensitive than controls to isoprenaline. In these tissues, prenalterol was a partial agonist producing 68% of the maximal response to isoprenaline. Schild regressions with atenolol indicated no change in beta-adrenoreceptors with IMX treatment and also that isoprenaline and prenalterol activated the same receptor in this tissue. The relative efficacy of isoprenaline and prenalterol was measured by using the KB estimated by Schild analysis for prenalterol and a Kd for isoprenaline from published binding studies. The relative efficacy of these drugs (epsilon ISO/epsilon PREN) was 242 +/- 29. The general method of potentiation of responses to weak agonists to estimate relative efficacy is discussed.
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PMID:The measurement of the relative efficacy of agonists by selective potentiation of tissue responses: studies with isoprenaline and prenalterol in cardiac tissue. 620 97

Triacylglycerol breakdown (lipolysis) results from a series of reactions culminated by activation of "hormone-stimulated" triacylglycerol lipase, an enzyme unique to adipose tissue. We have studied various components of the lipolytic process in human omental adipocyte precursors differentiating in culture. The levels of cyclic AMP, the "second messenger" of lipolytic hormones, were about sixfold higher in fat cell precursors than those in abdominal skin fibroblasts. L-Isoproterenol resulted in significant elevation of cyclic AMP levels in both cell types. Preincubation of intact adipocyte precursors with insulin resulted in significant enhancement of "low Km" cyclic AMP phosphodiesterase activity; in contrast, this hormone had no effect on fibroblast phosphodiesterase activity, a distinctive biochemical difference despite the morphological similarities between the two cell types during the early stages of adipocyte precursor maturation. Incubation of adipocyte precursors with isoproterenol resulted in the release of fatty acids into the medium, findings indicative of "hormone-stimulated" lipase activity and, hence, the operation of the entire "lipolytic cascade"; isoproterenol-stimulated lipolysis was inhibited by insulin. Release of fatty acids from fibroblasts was not observed. Thus, "hormone-stimulated" lipolysis and insulin stimulation of cyclic AMP phosphodiesterase activity are expressed during early stages of human adipocyte precursor differentiation.
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PMID:Cyclic AMP metabolism and lipolysis in cultured human adipocyte precursors. 624 74

The effects of ethanol, acetone and dimethylsulfoxide (DMSO) were tested on the accumulation of cyclic AMP in human peripheral blood lymphocytes in vitro. Isoproterenol (1.0X10(-8) - 1.0X10(-4)M), PGE2 (3X10(-8)-3X10(-6)M), adenosine (10(-7) - 10(-4)M) and phenylisopropyladenosine (10(-8) - 10(-4)M) caused a dose dependent increase in cyclic AMP accumulation. Over the entire range of concentration of stimulating drugs, ethanol caused an enhanced accumulation of cyclic AMP. At temperatures between 15 degrees and 30 degrees the effect of ethanol rose with increasing concentration from 0.2-6%. At 37 degrees and 40 degrees, 6% ethanol had less stimulatory effect than 2% ethanol. The effect of ethanol was shared by acetone and to a minor extent by DMSO, and was present also when phosphodiesterase was inhibited by isobutylmethylxanthine. It is suggested that ethanol enhances adenylate cyclase activity as a consequence of altered cell membrane fluidity. Since the effects on cyclic AMP accumulation can be observed already at rather low concentration of the solvents they may be of toxicological significance.
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PMID:Effects of ethanol on human lymphocyte levels of cyclic AMP. In vitro: Potentiation of the response to isoproterenol, prostaglandin E2 or adenosine stimulation. 624 71


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