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

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine 3',5-cyclic monophosphate (cAMP) was shown to stimulate insulin secretion from electrically permeabilised islets of Langerhans incubated in Ca2+/EGTA buffers. cAMP-induced insulin secretion occurred in the presence of either sub-stimulatory (50 nM) or stimulatory (greater than 100 nM) concentrations of Ca2+. Similar effects on secretion were obtained in response to 8-bromo-cAMP (8-Br-cAMP) or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine. Forskolin (0.2-20 microM) increased adenylate cyclase activity and enhanced insulin secretion from the permeabilised islets. These results suggest that, in electrically permeabilised islets, cAMP-induced insulin secretion is not dependent on changes in cytosolic Ca2+.
...
PMID:Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high-voltage discharge. 242 66

Cellular mechanisms underlying the anti-secretory actions of the prostaglandin E2 analogue enprostil were studied using enzyme-dispersed, elutriator-enriched canine parietal cells and the accumulation of the weak base 14C-labeled aminopyrine as a functional index. Enprostil inhibited the accumulation of aminopyrine stimulated by histamine and the phosphodiesterase inhibitor isobutylmethyl, but not by carbachol, gastrin, or dibutyryl cyclic adenosine monophosphate. Inhibition by enprostil was dose-dependent (0.1 nM to 1 microM), with maximal inhibition ranging from 65 to 95 percent. Over the same concentration range, enprostil inhibited the histamine-stimulated generation of cyclic adenosine monophosphate. This selective inhibition of histamine activation of parietal cell function was comparable to that found for prostaglandin E2. Forskolin, a diterpene that directly activates the catalytic subunit of adenylate cyclase, was also markedly inhibited by nanomolar concentrations of prostaglandin E2 and enprostil. We conclude that at least a component of the secretory inhibition by enprostil reflects direct interference with histamine stimulation of parietal cell adenylate cyclase.
...
PMID:Prostanoid inhibition of canine parietal cells. 242 41

Forskolin, a plant cardiotonic diterpene, stimulated proteoglycan biosynthesis by chondrocytes in monolayer culture. The quantitative increase in proteoglycans was dependent on the concentration of forskolin, but was relatively independent of the presence of serum. At forskolin concentrations that stimulated proteoglycan synthesis, a significant stimulation of adenylate cyclase and cAMP was also measured. The quantitative increase in proteoglycans was characterized, qualitatively, by an increased deposition of newly synthesized proteoglycan in the cell-associated fraction. An analysis of the most dense proteoglycans (fraction dA1) in the cell-associated fraction showed that more of the proteoglycans eluted in the void volume of a Sepharose CL-2B column, indicating that an increased amount of proteoglycan aggregate was synthesized in forskolin-treated cultures. The proteoglycan monomer dA1D1 secreted into the culture medium of forskolin-stimulated cultures overlapped in hydrodynamic size with that of control cultures, although cultures stimulated with forskolin and phosphodiesterase inhibitors produced even larger proteoglycans. The hydrodynamic size of 35SO4 and 3H-glucosamine-labelled glycosaminoglycans isolated from the dA1D1 fraction of the culture medium was greater in forskolin-treated chondrocytes, especially from those in which phosphodiesterase inhibitors had been added. These results indicated that forskolin, a direct activator of chondrocyte adenylate cyclase mimicked the effects of cAMP analogues on chondrocyte proteoglycan synthesis previously reported. These results implicate activation of adenylate cyclase as a regulatory event in the biosynthesis of cartilage proteoglycans, and more specifically in the production of hydrodynamically larger glycosaminoglycans.
...
PMID:Stimulation of sulfated-proteoglycan synthesis by forskolin in monolayer cultures of rabbit articular chondrocytes. 242 22

The effect of adenylate cyclase inhibitors and activators on enzyme kinetics and cyclic AMP (cAMP) levels was determined in the bullfrog retinal pigment epithelium (RPE). The RPE enzyme has two Km for ATP: 5.2 X 10(-4) and 4.0 X 10(-5) M, with Vmax of 2.5 and 0.25 nmol X mg protein-1 X min-1. Forskolin, the most potent activator, produced a fourfold increase in enzyme activity and, in the presence of isobutylmethylxanthine (IBMX), an inhibitor of phosphodiesterase, caused a 20-fold increase in cAMP levels. Alloxan, a potent inhibitor, blocked the forskolin-induced activation of this enzyme. In the isolated RPE choroid, forskolin (plus IBMX) produced changes in membrane voltage and resistance that were similar in magnitude but slower in time course than those produced by exogenous cAMP. Like exogenous cAMP, forskolin also decreased steady-state fluid and solute transport in isotonic proportions. Therefore, modulation of RPE adenylate cyclase activity plays an important role in the control of RPE transport.
...
PMID:Adenylate cyclase stimulation alters transport in frog retinal pigment epithelium. 243 82

The mechanism by which tripeptide aldehyde proteinase inhibitors decrease prolactin (PRL) and growth hormone (GH) secretion was studied. Agents known to modify the intracellular levels of cyclic adenosine monophosphate (cAMP) or cytosolic free calcium were used in monolayer cultures of the rat anterior pituitary gland. The phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), 8-bromo-cAMP and forskolin all stimulated PRL release. Boc-D-Phe-Pro-arginal (Boc-DPPA) at 1 mmol/l concentration was a potent inhibitor of basal PRL release and significantly decreased the effect of 8-Br-cAMP, forskolin or IBMX (0.5 mmol/l). Forskolin (1 mumol/l) stimulated ACTH, PRL and GH release and all these effects were decreased by 100 mumol/l of Boc-D-Phe-Phe-lysinal (Boc-DPPL). Neither tripeptide aldehyde affected the forskolin-induced rise in intracellular cAMP. Growth hormone releasing factor (hpGRF, 1 nmol/l) stimulated both GH release and intracellular cAMP generation; Boc-DPPL (100 mumol/l) significantly decreased stimulated GH release without affecting cAMP accumulation. Increasing medium K+ to 10 times normal level stimulated PRL release presumably by enhancing Ca2+ entry into the cells and 1 mmol/l Boc-DPPA decreased high potassium-stimulated PRL release. The ionophore A-23187 stimulated PRL release at 10 mumol/l but not at 1 mumol/l. At 1 mumol/l A-23187 prevented the Boc-DPPA-induced inhibition of PRL release. These findings suggest that the tripeptide aldehyde proteinase inhibitors inhibit PRL and GH release at a site beyond cAMP formation.
...
PMID:Is calcium or cyclic AMP involved in the inhibitory effect on pituitary hormone secretion of the tripeptide aldehyde proteinase inhibitors? 244 48

The effects of the adenylate cyclase activator forskolin upon voltage-activated K(V) currents were investigated in Helix nerve cells. Forskolin induced a fast concentration-dependent inactivation of K(V) currents without modifying the activation kinetics. The induced fast inactivation did not result from a speeding up of the voltage-controlled slow inactivation; it could not be mimicked by intracellular injection of cAMP and it was not potentiated by inhibition of the phosphodiesterase. The forskolin induced K current relaxation can be simulated by a model assuming that the drug binds reversibly to open K channels with a dissociation constant of 16.4 microM.
...
PMID:Forskolin interaction with voltage-dependent K channels in Helix is not mediated by cyclic nucleotides. 244 76

Forskolin, an activator of adenylate cyclase, was used to examine the regulation of [3H]acetylcholine (ACh) release by cyclic AMP (cAMP)-related mechanisms in myenteric plexus-longitudinal muscle preparations of guinea pig small intestine. Forskolin evoked a dose-related increase in [3H]ACh release. Both dibutyryl-cAMP and 8-Br-cAMP significantly elevated [3H]ACh secretion. In the presence of phosphodiesterase inhibitors (theophylline and 3-isobutyl-1-methylxanthine), the basal [3H]ACh output was increased. There was a significantly greater stimulation when forskolin was used to incite endogenous cAMP synthesis and phosphodiesterase inhibitors were simultaneously applied to prevent cAMP breakdown. The enhancement of forskolin-stimulated release by theophylline or 3-isobutyl-1-methylxanthine strongly implicates a synergistic interaction between the two. These findings suggest that forskolin acts to increase ACh release by a modulation of endogenous cAMP and further support a cAMP-mediated mechanism in the secretion of ACh from myenteric cholinergic neurons.
...
PMID:Stimulation of acetylcholine release from myenteric neurons of guinea pig small intestine by forskolin and cyclic AMP. 244 53

Immunologic activation of purified human lung mast cells (HLMC) and basophils with anti-IgE induced histamine release but failed to elicit any changes in cAMP levels. In contrast, histamine release and monophasic rises in cAMP were observed in both rat peritoneal mast cells (RPMC) challenged with concanavalin A (73% enhancement over basal cAMP 20 sec after activation) and a cultured mouse bone marrow-derived mast cell (PT18 cell line) passively sensitized with dinitrophenol-specific IgE and stimulated with antigen (39% increase above basal at 15 sec). The adenylate cyclase activators isoprenaline, prostaglandin E2 (PGE2), and forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) all induced elevations in cAMP levels in both basophils and HLMC. In basophils, PGE2 and isoprenaline produced approximately twofold increases in cAMP that were maximal at 1 min and decayed thereafter. Forskolin and IBMX produced threefold increases in cAMP that peaked 10 min after activation and persisted for up to 20 min. In HLMC, isoprenaline provoked a rapid monophasic fourfold increase in cAMP that was maximal at 1 min after addition. Levels of cAMP subsequently declined but remained significantly elevated over resting levels for up to 30 min. PGE2, forskolin, and IBMX all produced approximately threefold rises in HLMC cAMP that peaked around 5 min and persisted for 30 min. In both the basophil and HLMC, agonist-induced elevations in cAMP correlated well with the inhibition of mediator release. In basophils, the order IBMX greater than forskolin greater than PGE2 greater than isoprenaline held for both the inhibition of histamine and leukotriene C4 release and the augmentation of cAMP levels. In HLMC, individual agonists elevated cAMP levels to similar degrees and inhibited the release of histamine, leukotriene C4, and PGD2 to comparable extents, although the release of the arachidonate metabolites was generally more sensitive to the inhibitory actions of these agonists. These results suggest that elevations in cAMP, in both the basophil and HLMC, are associated with the inhibition of mediator release but not the initiation of the secretory process.
...
PMID:Regulation of human basophil and lung mast cell function by cyclic adenosine monophosphate. 244 82

Pial arterioles of living mice anesthetized with urethane were monitored by television microscopy. I tested the existence of an adenylate cyclase-cyclic adenosine monophosphate (cAMP) system for dilating the arterioles by topically applying the following drugs: cAMP (10(-3) M), its more potent analogue dibutyryl cAMP (10(-3) and 10(-4) M), and forskolin (10(-6) M). Forskolin activates endogenous adenylate cyclase, which leads to increases in endogenous cAMP. Each drug was applied for 30 seconds; all three produced dilation. I then applied either cAMP or forskolin in the presence or absence of 10(-4) M isobutylmethylxanthine (IMX), an inhibitor of endogenous phosphodiesterase, which destroys cAMP. The presence of IMX significantly potentiated the dilation produced by exogenous cAMP and forskolin. These data indicate that cerebral surface arterioles of mice respond to cAMP with dilation and contain the enzymes for producing and inactivating this dilator. The existence of an adenylate cyclase-cAMP dilating mechanism in pial arterioles does not rule out the simultaneous existence of other dilating mechanisms.
...
PMID:In vivo evidence that an adenylate cyclase-cAMP system dilates cerebral arterioles in mice. 253 12

K+ channels in the membrane of murine pancreatic beta-cells were studied using the patch-clamp technique. The delayed outward current was activated in whole-cell experiments by depolarizing voltage pulses to potentials between -30 mV and 0 mV. Forskolin blocked the current rapidly (less than 5 s) and reversibly with 50% inhibition at 13 microM. The inhibition did not depend on a stimulation of the adenylate cyclase since it occurred even in presence of 1 mM cAMP in the pipette solution which replaced the cytoplasm. Membrane permeant cAMP analogues and phosphodiesterase inhibitors did not influence the delayed outward current. In experiments on outside-out patches forskolin (100 microM) shortened the openings of a channel of about 10 pS conductance at 0 mV and a time course of activation and inactivation similar to the whole-cell current. Another smaller, slowly activating channel and the Ca2+- and ATP-dependent K+ channels were influenced only weakly or not at all. It is therefore concluded that the 10-pS channel generates most of the delayed outward K+ current in murine pancreatic beta-cells. The Ca2+-independent part of the delayed outward current in bovine adrenal chromaffin cells was also blocked by forskolin (100 microM).
...
PMID:Forskolin-induced block of delayed rectifying K+ channels in pancreatic beta-cells is not mediated by cAMP. 245 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---