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 AtT-20/D16-16 mouse pituitary tumor cell secretes corticotropin (ACTH) in response to corticotropin-releasing factor (CRF), (-)-isoproterenol, and vasoactive intestinal peptide (VIP). These responses are associated with a rapid increase in cyclic AMP formation. Somatostatin (SRIF) markedly decreases the stimulatory effect of CRF, (-)-isoproterenol, and VIP on both cyclic AMP formation and immunoreactive ACTH secretion. Forskolin and cholera toxin, adenylate cyclase activators, also stimulate cyclic AMP formation and ACTH secretion in AtT-20 cells and these responses are all inhibited by SRIF. The ACTH secretory responses to melittin and to the calcium ionophore A23187, neither of which increases cyclic AMP in AtT-20 cells, were not inhibited by SRIF. SRIF did not affect the binding of a tritiated beta-adrenergic receptor antagonist to AtT-20 membranes nor did it decrease basal cyclic AMP formation even in the presence of excess phosphodiesterase inhibitor, indicating that the reduction of cyclic AMP levels by SRIF did not involve either an interference with beta-adrenergic agonist binding to receptors or stimulation of cyclic AMP degradation. These results indicate that the inhibition of CRF-, (-)-isoproterenol-, and VIP-stimulated ACTH secretion by SRIF may be regulated by its inhibitory action on adenylate cyclase.
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PMID:Somatostatin inhibits multireceptor stimulation of cyclic AMP formation and corticotropin secretion in mouse pituitary tumor cells. 612 32

Serotonin release from rabbit enterochromaffin cells located in the mucosal epithelium of the small intestine was studied in vitro. Serotonin release from both the serosal and mucosal sides of the small intestine was measured. The addition of muscarinic but not nicotinic cholinergic agonists to the serosal medium resulted in a large but transient increase in serotonin release from the serosal but not the mucosal side of the intestine. Mucosal addition of these agents was ineffective. Serotonin release stimulated by the cholinergic agonist carbachol appeared to be dependent upon influx of extracellular Ca++ for the following reasons: 1) depletion of serosal Ca++ inhibited carbachol-stimulated release; 2) carbachol-stimulated serotonin release was blocked by the inorganic calcium channel blockers Co++, Ni++, Cd++, La and Gd; and 3) serosal serotonin release was increased by the Ca++ ionophore, ionomycin, and by Ba++. The addition of 8-bromoadenosine cyclic AMP or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, to the serosal medium produced a sustained elevation of serosal serotonin release. 8-bromoadenosine-cyclic AMP-stimulated release was not blocked by depleting extracellular Ca++. Forskolin, a compound which stimulates adenylate cyclase, also stimulated serosal serotonin release. 8-bromoadenosine-cGMP had no effect on serotonin release. Somatostatin (10(-8)-10(-6) M) caused a dose-dependent inhibition of carbachol-stimulated serotonin release. Somatostatin (10(-6) M) only partially inhibited serotonin release stimulated by 8-bromoadenosine-cyclic AMP, 3-isobutyl-1-methylxanthine and forskolin and had no effect on release stimulated by Ba++. The results suggest potential roles for both calcium and cyclic nucleotides in the regulation of serotonin release.
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PMID:Regulation of serotonin release from rabbit intestinal enterochromaffin cells. 614 Mar 9

The diterpene, forskolin, is a potent and reversible inhibitor of progesterone-induced meiosis in Xenopus laevis oocytes (ED50 of inhibition approximately 3 microM). Forskolin alone increases cAMP concentration in oocytes, but, unlike with cholera toxin treatment, there is no lag phase, and reversibility is obtained by washing the cells. Progesterone decreases the forskolin effect on cAMP accumulation, but cAMP concentration remains above the level observed in oocytes treated with progesterone alone. The data corroborate the previously-established antagonistic effect of cAMP on progesterone-induced meiosis. Preliminary experiments in the presence of a phosphodiesterase inhibitor suggest that, as in other biological systems, forskolin is an activator of adenylate cyclase in xenopus laevis oocytes. Contrary to what is observed when forskolin is present in the incubation medium, no effect of the diterpene is recorded after its injection into oocytes, evoking a site of action at the external side of the membrane.
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PMID:Forskolin increases cAMP and inhibits progesterone induced meiosis reinitiation in Xenopus laevis oocytes. 618 Aug 91

Mouse oocytes are reversibly inhibited from resuming meiotic maturation in vitro by cAMP phosphodiesterase inhibitors such as 3-isobutyl-1-methyl xanthine (IBMX) and cAMP analogs such as dibutyryl cAMP (dbcAMP). Oocytes cultured in IBMX-containing medium were transferred to and cultured in IBMX-free medium for various periods of time prior to their return to either IBMX- or dbcAMP-containing medium. Results from these experiments defined a period of time in which oocytes became committed to resuming meiosis. Forskolin, which elevated the intracellular oocyte cAMP concentration, transiently inhibited oocytes from resuming meiosis. Levels of cAMP were determined in oocytes incubated in medium that allows resumption of meiosis. The level of oocyte cAMP decreased significantly during the time in which oocytes become committed to resuming meiosis. This decrease in oocyte cAMP was not observed in oocytes inhibited from resuming meiosis by IBMX. In addition, cAMP levels were determined in preovulatory antral follicles, cumulus cell-oocyte complexes, and oocytes during gonadotropin-induced resumption of meiosis in vivo. A decrease in oocyte cAMP preceded resumption of meiosis as manifested by germinal vesicle breakdown (GVBD). This decrease apparently occurred before or during a period of time in which follicle and cumulus cell cAMP were increasing. Associated with commitment to resume meiosis was a characteristic set of changes in oocyte phosphoprotein metabolism that preceded GVBD. These changes are, to date, some of the first reported biochemical changes that precede GVBD. Results from these experiments are discussed in terms of a possible role cAMP may play in regulation of resumption of meiosis in mammals.
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PMID:Regulation of mouse oocyte meiotic maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. 618 52

Forskolin, a diterpene that activates rapidly adenylate cyclase activity in several somatic cell systems, prevents spontaneous meiotic maturation of denuded mouse oocytes (ED50 of inhibition approximately 2.5 microM), unlike cholera toxin. The oocyte is sensitive to the action of forskolin during the period preceding germinal vesicle breakdown (GVBD). Washing of the cells abolishes the effect. The diterpene potentiates the inhibitory effect of iso-butyl-methyl-xanthine (IBMX), a phosphodiesterase inhibitor, and it increases cAMP concentration in the oocytes. These findings not only confirm the antagonistic effect of cAMP on the first step of meiosis reinitiation (GVBD) in mammalian oocytes, but also provide the first demonstration of a functional adenylate cyclase system in mammalian oocytes upon which regulatory signals may act.
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PMID:Inhibition of denuded mouse oocyte meiotic maturation by forskolin, an activator of adenylate cyclase. 619 69

Methylisobutylxanthine (MIX) raised cAMP levels and inhibited prostacyclin synthesis and arachidonic acid release in endothelial cells from both pig aorta and human umbilical vein. These effects were reversible and dose dependent on MIX concentrations. Dibutyryl cAMP (3 mM) alone did not inhibit prostacyclin synthesis or arachidonic acid release. When added with MIX, dibutyryl cAMP did not enhance the inhibition elicited by MIX. MIX inhibited the formation of lysophospholipids, 1,2-diacylglycerol and phosphatidic acid in bradykinin-stimulated pig endothelial cells, suggesting that the inhibition of prostacyclin synthesis resulted from an apparent inhibition of both phospholipase A2 and phospholipase C. Other phosphodiesterase inhibitors, theophylline and mopidamole, also raised cAMP levels and inhibited arachidonic acid release. However, there was no correlation between cAMP levels and these inhibitions. Forskolin, an adenylate cyclase activator, elevated intracellular cAMP levels with no apparent inhibition on prostacyclin synthesis. We conclude that the inhibitory effect of MIX on phospholipase A2 and phospholipase C is probably through mechanisms other than the elevation of the cAMP level.
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PMID:Inhibition of prostacyclin synthesis in endothelial cells by methylisobutylxanthine is not mediated through elevated cAMP level. 619 92

We have examined the roles that cyclic AMP and protein synthesis play in the development of refractoriness in C6-2B rat glioma cells using the diterpene, forskolin, a general activator of cyclic AMP-generating systems. Forskolin-stimulated cyclic AMP accumulation peaked at 30 min and declined thereafter to 10% of peak levels by 3 hr despite the continued presence of sufficient forskolin to produce 98% of the control response when the incubation medium was transferred to naive cells. C6-2B cells treated for 3 hr with forskolin were refractory to a subsequent challenge with forskolin or isoproterenol. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) increased the degree of refractoriness developed after forskolin treatment. In the presence of IBMX, the induction of refractoriness by forskolin and forskolin-stimulated cyclic AMP accumulation were similarly dependent on forskolin concentration. Pre-treatment with isoproterenol or the cyclic AMP analogue, dibutyryl cyclic AMP, induced refractoriness to forskolin. When C6-2B cells were pre-treated with forskolin plus the protein synthesis inhibitor, cycloheximide, the development of refractoriness to forskolin or isoproterenol was attenuated. Cycloheximide prevented isoproterenol- or dibutyryl cyclic AMP-induced refractoriness to forskolin. These data provide further evidence that the onset of the refractory state in C6-2B cells is mediated by cyclic AMP and is a protein synthesis-requiring process.
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PMID:Forskolin-stimulated cyclic AMP accumulation mediates protein synthesis-dependent refractoriness in C6-2B rat glioma cells. 619 88

The role of adenosine 3',5'-cyclic monophosphate (cAMP) in the release of noradrenaline from central neurones has been investigated by examining the effects of forskolin, 3-isobutyl-l-methylxanthine (IBMX), cis-6-(p-acetamidophenyl)-1,2,3,4,4a, 10b-hexahydro-8,9-dimethoxy-2-methyl-benzo[c] [1,6]-naphthyridine bis (+ +hydrogenmaleinate) (AH21-132; a new phosphodiesterase inhibitor) and N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphate (dibutyryl-cAMP) on the outflow of tritiated compounds from rat and rabbit cerebral cortex slices preincubated with [3H]-noradrenaline. Forskolin, IBMX, AH21-132 and dibutyryl-cAMP produced a concentration-dependent increase in both basal and electrically-evoked efflux of tritium from rat and rabbit cortex slices. The increase in basal tritium efflux from rabbit cortex slices elicited by forskolin and IBMX could be attributed mainly to an increase in [3H]-DOPEG although a small increase in [3H]-noradrenaline was also observed. Forskolin and (when combined with noradrenaline) IBMX and AH21-132 increased the cAMP content of rat cortex slices at similar or somewhat higher concentrations that they increased tritium efflux. Neither forskolin nor IBMX or AH21-132 had any effect on the cocaine-sensitive uptake of [3H]-noradrenaline into synaptosomes prepared from rat or rabbit cortex. The effects of forskolin, IBMX and dibutyryl-cAMP on electrically-evoked overflow of tritium from rat and rabbit cortex slices were reduced when cocaine (10 microM) was present in the superfusion medium, although forskolin produced a similar increase in cAMP in the absence or presence of cocaine. It is suggested that cAMP may facilitate the normal process of noradrenaline release by nerve stimulation.
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PMID:Forskolin and the release of noradrenaline in cerebrocortical slices. 620 Jul 82

Octopamine increases the level of cyclic AMP in a dose-dependent way in the locust extensor tibiae neuromuscular preparation. The response peaks after a 10 min exposure and then declines to a plateau. The effect of octopamine is potentiated in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The levels of cyclic GMP in the muscle were not affected by octopamine. The response is stereospecific for the naturally occurring D(-) isomer of octopamine and is also specific for monophenolic biogenic amines. Studies with a range of synthetic agonists and antagonists reveal that the receptors mediating the response are of the OCTOPAMINE2 class. Forskolin, a diterpene activator of adenylate cyclase activity, increases cyclic AMP but not cyclic GMP levels in the extensor muscle. The response has a prolonged time course and is again potentiated by IBMX. Stimulation of the octopaminergic neurone to the extensor muscle increases the levels of cyclic AMP but not those of cyclic GMP. The response is blocked by phentolamine, an alpha-adrenergic blocking agent that also blocks the effects of octopamine in this preparation. The results are discussed in terms of the parallels between the biochemical and physiological effects of octopamine on this muscle and in terms of the mode of action of the octopamine receptors present.
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PMID:A modulatory octopaminergic neurone increases cyclic nucleotide levels in locust skeletal muscle. 620 9

Isolated salivary glands of the cockroach Nauphoeta cinerea Olivier secrete fluid in response to nerve stimulation or application of dopamine, the acinar cells undergoing a hyperpolarization during secretion. The aim of the present work was to examine whether cyclic AMP acts as a second messenger in the acinar cells to cause the secretory and electrical responses to the transmitter dopamine. Cyclic AMP (10-500 microM) in the bathing solution of isolated glands caused a dose-dependent secretory response but no change in the membrane potential of acinar cells. The time courses and magnitudes of the secretory responses to cyclic AMP resembled those features of responses to dopamine. Forskolin, an adenylate cyclase activator, caused fluid secretion but the responses were small and irregular. The phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine (IBMX)(1-1000 microM) produced fluid secretion in a dose-dependent manner, the maximal response being equal to that of dopamine. Maintained responses to cyclic AMP or IBMX required the presence of extracellular calcium ions. An inhibitor (MDL 12,330A) of adenylate cyclase suppressed the secretory responses to dopamine, cyclic AMP, IBMX, the ionophore A23817 or the readmission of calcium ions to the bathing solution; this inhibitor did not block the acinar hyperpolarization caused by nerve stimulation. Cyclic AMP stimulation of glands, bathed in chloride-free solution to prevent fluid secretion, produced a change in the gland cells which outlasted the period of exogenous cyclic AMP stimulation and expressed itself as a transient secretion upon return of the normal bathing solution. It was concluded that stimulus-secretion coupling in this gland involves a calcium-dependent second messenger system and that cyclic AMP is probably the second messenger. The evidence did not support the idea that cyclic AMP is also a second messenger for the acinar cell hyperpolarization evoked by nerve stimulation.
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PMID:Cyclic AMP as a possible mediator of dopamine stimulation of cockroach gland cells. 620 44


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