Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of dog thyroid slices with 1 mU/ml TSH resulted in enhanced intracellular and extracellular cAMP accumulation. In the absence of TSH, the intra- and extracellular cAMP concentrations remained at a constant low level. The release of cAMP from TSH-stimulated slices was inhibited by 10 microM PGA1, 1 mM probenecid or 1 mM IBMX, which are known inhibitors of cAMP escape in several tissues. Negative controls of intracellular cAMP levels are exerted in the dog thyroid by 10 microM carbamylcholine (shown to activate a Ca++- calmodulin dependent phosphodiesterase), 100 microM norepinephrine and 100 microM iodide (both inhibiting adenylate cyclase activity). The purpose of the present study was to demonstrate that these three agents do not enhance cAMP escape. The results presented here show that these agents decrease both intracellular accumulation and escape in parallel. Moreover, the escape constants obtained by numerical simulation were not greater in the presence of inhibiting concentrations of carbamylcholine, norepinephrine or iodide. Thus the inhibition by these agents of cAMP accumulation in TSH-stimulated dog thyroid slices cannot be explained by a stimulation of cAMP escape from these cells.
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PMID:The escape of cyclic AMP from dog thyroid slices exposed to positive and negative regulators. 242 18

1. Membrane currents were recorded from voltage clamped Xenopus laevis oocytes, still surrounded by follicular cells, theca and enveloping inner ovarian epithelia (ovarian follicles). 2. Superfusing follicles with frog Ringer solution containing E-series prostaglandins (PGE1 or PGE2) or oxytocin (0.5-2 microM) generated slow membrane currents arising from an increase in membrane conductance to K+. 3. Follicles taken from different frogs varied greatly in responsiveness to PGE and oxytocin. For example, enclosed oocytes with good sensitivity to prostaglandins responded to 1 nM-PGE, whereas follicles from some frogs failed to respond at 5 microM. 4. Oocytes with good responsiveness to PGE also produced K+ currents to PGA1, PGA2, PGB1, 11-deoxy-PGE1 and 11-beta-PGE2, whereas PGF2 alpha, PGI2, PGD2 and 8-iso-PGE1 generally failed to elicit membrane currents. 5. Responses to PGE and oxytocin were mimicked by the adenylate cyclase activator forskolin or by intraoocyte pressure injection of cyclic nucleotides. Responses were potentiated by the phosphodiesterase inhibitors theophylline and 3-isobutyl-1-methylxanthine (IBMX). In IBMX (0.5 mM), human atrial natriuretic factor (ANF) (10-60 nM) elicited a similar K+ conductance. This all implied that cyclic nucleotides played a role in the receptor-channel coupling mechanism of these responses. 6. Defolliculating oocytes effectively abolished responses to prostaglandins, oxytocin and ANF, suggesting that the currents arise in follicular cells. 7. The responses of PGE, oxytocin and ANF thus resembled currents elicited by catecholamines, adenosine, gonadotrophins and vasoactive intestinal peptide (VIP). However, PGE, oxytocin and ANF responses were not blocked by catecholaminergic or purinergic antagonists. Moreover, when comparing follicles isolated from different frogs, the sensitivity to PGE and oxytocin varied independently of that to gonadotrophin or VIP. These experiments suggest that Xenopus ovarian follicles contain specific and distinct receptors for PGE, oxytocin and ANF. 8. Acetylcholine attenuated the cyclic nucleotide-mediated K+ responses, including currents elicited by PGE, oxytocin and ANF. Attenuation was not dependent on, or mimicked by, activation of the inositol phosphate-diacylglycerol messenger pathways located in the oocyte itself, nor was it appreciably blocked by loading follicle-enclosed oocytes with 0.1-1.5 mM-EGTA.
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PMID:Membrane currents elicited by prostaglandins, atrial natriuretic factor and oxytocin in follicle-enclosed Xenopus oocytes. 248 34

We have been investigating the hypothesis that prostaglandins including prostaglandin E2 (PGE2) produced during the critical condensation phase of limb chondrogenesis are involved in the regulation of cartilage differentiation by acting as local modulators of cyclic AMP (cAMP) accumulation. The purpose of the present study was to determine directly whether PGE2 and other prostanoids which had previously been shown to stimulate in vitro chondrogenic differentiation do indeed elevate the cAMP content of limb mesenchymal cells, and to determine whether the ability of various prostanoids to increase cAMP production by these cells directly reflects the potencies of these same molecules in stimulating chondrogenesis. We have found that PGE2 does indeed elicit a striking elevation in the cAMP content of subridge mesenchymal cells, indicating that the cells possess adenylate cyclase-coupled receptors for this molecule. The effect of PGE2 on cAMP accumulation is potentiated by a phosphodiesterase inhibitor, thus paralleling the potentiating effect phosphodiesterase inhibitors have on PGE2-stimulated in vitro chondrogenesis. The effect of PGE2 on cAMP content is dose-dependent with a 3-fold increase seen at 10(-8)M, which is the lowest concentration at which PGE2 effectively stimulates chondrogenesis. PGE1, which is just as effective as PGE2 in stimulating chondrogenesis, is just as effective as PGE2 in stimulating cAMP accumulation. PGA1, which is a much less effective stimulator of chondrogenesis than PGE2 or PGE1, is less than half as potent as these molecules in elevating cAMP levels. PGF1 alpha, 6-keto PGF1 alpha, and thromboxane B2, which have little or no effect on chondrogenesis, have little or no effect on cAMP content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of prostaglandins on the cyclic AMP content of limb mesenchymal cells. 299 86

Platelet aggregation plays a major role in thrombogenesis. This study was undertaken to examine the inhibition of platelet aggregation induced by adenosine diphosphate. It is known that cyclic AMP (adenosine monophosphate) and its dibutyryl derivative inhibit platelet aggregation. This study showed that prostaglandin E1 (PGE1) also inhibits platelet aggregation and stimulates cyclic AMP synthesis by stimulation of adenyl cyclose. Caffeine, on the other hand, inhibits platelet phosphodiesterase, and increases cyclic AMP levels. PGA1 and PGF1 alpha can also inhibit platelet aggregation but only at very high concentrations.
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PMID:Platelet aggregation. I. Regulation by cyclic AMP and prostaglandin E1. 431 Jan 50

The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic glucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1 greater than PGE1 greater than PGB1 greater than PGF2 alpha. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virus-stimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormone-like substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.
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PMID:Role of natural prostaglandins in the control of murine mammary tumor virus expression. 628 Dec 84

A variety of studies indicate that a key event in limb chondrogenic differentiation is a cellular condensation process during which an intimate cell-cell interaction occurs that triggers cartilage differentiation by elevating cAMP levels. It has recently been demonstrated that when limb mesenchymal cells are subjected to high density monolayer culture under conditions conducive to chondrogenesis, they synthesize several prostaglandins, including PGE2 and prostacyclin, which are important local modulators of cAMP formation in a number of cells and tissues. In the present study, we demonstrate that exogenous PGE2 stimulates the in vitro chondrogenic differentiation of the subridge mesoderm of the embryonic chick limb bud. The stimulatory effect of PGE2 is greatly potentiated by the phosphodiesterase inhibitor, theophylline, suggesting its influence on chondrogenesis is mediated by its ability to increase cAMP levels. The stimulatory effect of PGE2 is dose-dependent and can be detected at a concentration as low as 10(-8)M. PGE1 is just as effective as PGE2 in stimulating in vitro chondrogenesis, whereas PGA1 and PGF1 alpha are less than half as effective. Thromboxane B2 has no effect on chondrogenesis. On the basis of our results, the possibility that endogenous prostaglandins might regulate limb cartilage differentiation by acting as local regulators of cAMP content is discussed.
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PMID:The effect of prostaglandins on in vitro limb cartilage differentiation. 630 16