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 purpose of this study was to try to differentiate histochemically between the various enzymes which may catalyze the hydrolysis of ATP in developing rat dental tissues. Freeze cut and freeze dried sections of molar and incisor teeth were incubated in lead capture-based media at pH 5.0, 7.2 or 9.4 with one of the following substrates: beta-glycerophosphate, AMP, ADP, ATP, AMP-PNP and tetrasodium pyrophosphate. To establish the enzymatic nature of the hydrolysis parallel sections were incubated after prior fixation in either formaldehyde or glutaraldehyde. By comparing the enzymatic stainings obtained with the various substrates and at the different pH:s, it was concluded that ATP can be visibly hydrolyzed in rat dental tissues by alkaline phosphatase (stratum intermedium, apical part of maturation ameloblasts, basal part of all ameloblasts, odontoblasts and subodontoblastic layer), specific ATPase (apical and basal parts of secretory ameloblasts) and ATP pyrophosphatase and/or adenylate cyclase (stratum intermedium, odontoblasts). Acid phosphatase, specific ADPase, 5'-nucleotidase, inorganic pyrophosphatase, 3':5'-cyclic-AMP-phosphodiesterase and adenylate kinase on the other hand, seem not to be engaged in the ATP hydrolysis to such a degree as to complicate the interpretation of the histochemical staining. The alkaline phosphatase part of the ATP hydrolysis appeared to be rather insensitive to aldehyde fixation, while the hydrolysis effected by specific ATPase and ATP pyrophosphatase and/or adenylate cyclase was extinguished after fixation with formaldehyde for 4 h or glutaraldehyde for 10 min.
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PMID:Adenosine triphosphate hydrolysis in rat dental tissues. A histochemical study to differentiate the enzymes involved. 18 60

We have measured by radioimmunoassay the amount of total, free, and bound forms of cyclic AMP (cAMP) within the abdominal ganglion and in five identified cell bodies of neurons from Aplysia californica. In the abdominal ganglion the unbound (free) cAMP levels comprised approximately 25-30% of the total cAMP content under the unstimulated condition, i.e., bathed in high-magnesium saline. Under pharmacological conditions that blocked endogenous phosphodiesterase and activated adenylate cyclase, ganglionic free cAMP levels were elevated more than fourfold, while bound cAMP levels more than doubled. Freeze-substitution techniques were employed to facilitate isolation of individual cell bodies either before or after pharmacological manipulation of cAMP levels. The basal, free cAMP content of cells R2, LP1, R15, L11, and L2-L6 was in the range of 10-40 pmol/mg of cell protein, which accounted for approximately one-half of the total cAMP content per cell body. Determinations of individual cell volumes indicated that the basal, free cAMP concentrations ranged from 1 to 6 microM. Under the same pharmacological conditions that elevated ganglionic cAMP in levels, no changes were measured in either the free or the bound forms of cAMP in isolated cell bodies. Our results indicate that the cAMP elevation was compartmentalized within the neuropilar region of the ganglion, most likely within the processes of the nerve cells. Previous results demonstrated that cAMP injections into the same Aplysia neurons studied here induced a cAMP-activated sodium current, INa (cAMP). In this report we discuss the possibility that pharmacological elevation of cAMP within neuronal processes may reach concentrations similar to those produced by cAMP injections into somata.
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PMID:Compartmentalization of cyclic AMP elevation in neurons of Aplysia californica. 303 61

1. Sugar transport in the giant muscle cells of Balanus nubilus is accelerated during contractile activity and exposure to porcine insulin. The characteristics of hexose-transfer regulation in the giant muscle cells have been examined by studying the transport of 3-O-methylglucose (a non-metabolized sugar) in both intact giant fibres and fibres subjected to internal solute control by internal dialysis.2. Sugar transport in barnacle muscle is mediated by a saturable process which is inhibited by both phloretin and cytochalasin B. Insulin increases the capacity of the transport system with little effect on its apparent affinity for sugar. Under the same conditions insulin increases 3-O-methylglucose-displaceable cytochalasin B binding. The effects of insulin on transport are half-maximal at 5 muM-insulin and are abolished by both insulin antibody and phloretin. The intact barnacle releases an insulin-like material in response to a rise in blood glucose levels.3. Insulin increases the cyclic GMP (cGMP) content and reduces the cyclic AMP (cAMP) content of barnacle muscle. Experiments with fibres injected with aequorin show that insulin also lowers cytosolic ionized Ca levels. The changes in cyclic nucleotide levels induced by insulin precede the effects on sugar transport and cytosolic ionized Ca. During repetitive contractile activity, cAMP, cGMP and ionized Ca levels are raised.4. Agents which raise the cAMP content of barnacle muscle normally inhibit sugar transport. Dibutyryl cAMP also inhibits transport. Alterations in cytosolic ionized Ca levels in intact fibres are without effect on sugar transport. Nevertheless, stimulation of transport by insulin is blunted when cytosolic ionized Ca is lowered by intracellular injection of the Ca-chelating agent, EGTA.5. Sugar uptake in the internally dialysed fibre is inhibited by intracellular application of cAMP. Internal application of Ca and cGMP stimulate sugar uptake in the dialysed fibre. Cyclic AMP reduces the capacity of the transport system whereas Ca and cGMP increase the capacity of the saturable transfer system. Cyclic AMP and cGMP act at kinetically independent sites. Internal ATP (2 mM) inhibits sugar uptake in the dialysed fibre by some 40%, possibly through the production of cAMP.6. External insulin stimulates sugar uptake in the dialysed fibre even when ionized Ca levels are buffered using EGTA. Stimulation by insulin requires the presence of cytosolic ATP and is potentiated by internal application of 1 mM-GTP. In the dialysed fibre stimulation of transport by insulin is greater than that brought about by Ca and cGMP.7. The stimulation of transport by insulin in the intact fibre and its inhibition by dibutyryl cAMP are abolished by intracellular injection of Gpp(NH)p. Injection of intact fibres with GTPgammaS potentiates the stimulation of transport by insulin and renders insulin-activation of transport irreversible. Injection of intact fibres with ATPgammaS leads to the irreversible inhibition of transport.8. Injection of intact fibres with cAMP phosphodiesterase lowers cAMP levels close to zero and stimulates sugar transport. Application of insulin to diesterase-injected fibres still stimulates transport in the absence of altered cytosolic cAMP.
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PMID:Insulin regulation of sugar transport in giant muscle fibres of the barnacle. 630 27

Phototransduction in Drosophila is mediated by a G-protein-coupled phospholipase C transduction cascade in which each absorbed photon generates a discrete electrical event, the quantum bump. In whole-cell voltage-clamp recordings, cAMP, as well as its nonhydrolyzable and membrane-permeant analogs 8-bromo-cAMP (8-Br-cAMP) and dibutyryl-cAMP, slowed down the macroscopic light response by increasing quantum bump latency, without changes in bump amplitude or duration. In contrast, cGMP or 8-Br-cGMP had no effect on light response amplitude or kinetics. None of the cyclic nucleotides activated any channels in the plasma membrane. The effects of cAMP were mimicked by application of the non-specific phosphodiesterase inhibitor IBMX and the adenylyl cyclase activator forskolin; zaprinast, a specific cGMP-phosphodiesterase inhibitor, was ineffective. Bump latency was also increased by targeted expression of either an activated G(s) alpha subunit, which increased endogenous adenylyl cyclase activity, or an activated catalytic protein kinase A (PKA) subunit. The action of IBMX was blocked by pretreatment with the PKA inhibitor H-89. The effects of cAMP were abolished in mutants of the ninaC gene, suggesting this nonconventional myosin as a possible target for PKA-mediated phosphorylation. Dopamine (10 microM) and octopamine (100 microM) mimicked the effects of cAMP. These results indicate the existence of a G-protein-coupled adenylyl cyclase pathway in Drosophila photoreceptors, which modulates the phospholipase C-based phototransduction cascade.
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PMID:Modulation of the light response by cAMP in Drosophila photoreceptors. 1051 99

Blast-induced tinnitus, along with associated auditory impairment and traumatic brain injury, is a primary concern facing military service members. To search for treatment, we investigated the therapeutic effects of sildenafil, a phosphodiesterase-5 inhibitor, given its vasodilatory effects and evidence suggesting its beneficial effects on noise-induced hearing loss. Rats were subjected to three consecutive blast exposures at 22 psi and were monitored for tinnitus using a gap-detection acoustic startle reflex paradigm. Hearing thresholds and detection were tested using auditory brainstem responses and prepulse inhibition, respectively. Blasted rats were either treated with sildenafil or tap water following blast exposure, while age-matched sham control rats were treated with sildenafil and no blast exposure. Our results showed that sildenafil did not effectively prevent acute tinnitus onset and hearing impairment. Instead, sildenafil significantly suppressed high-frequency tinnitus from 3 to 6 weeks after blast exposure and reduced hearing impairment during the first week after blast exposure. Complex results were observed in the startle force data, where sildenafil-treated rats displayed significantly reduced startle force compared to the untreated blasted group, suggesting possible mitigation of traumatic brain injury and suppression of hyperacusis-like percepts. Taken together, sildenafil showed a therapeutic effect on blast-induced tinnitus and audiological impairment in a time-dependent manner. Other regimens such as higher dosage prior to blast exposure and combination with other treatments deserve further investigation to optimize the therapeutic effects.
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PMID:Therapeutic effect of sildenafil on blast-induced tinnitus and auditory impairment. 2466 45