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)

Effect of serotonin on generation of the feeding rhythm in buccal ganglia was studied in 8 species from 3 subclasses of gastropod molluscs. Serotonin (10(-5) mol/l) initiated or increased the rhythmical activity in the buccal ganglia. The effect of serotonin was potentiated with theophylline (phosphodiesterase inhibitor).
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PMID:[Effect of serotonin and theophylline on generation of rhythmic activity in the buccal ganglia of gastropod mollusks]. 687 35

Glaucine and two of its structural analogues exerted an inhibitory effect on phosphodiesterase activity in different tissue homogenates. In experiments on rats glaucine applied intraperitoneally significantly increased the brain level of dopamine (DA) and did not change the content of noradrenaline and serotonin (5-HT). The combined application of L-DOPA and glaucine or glaucine derivatives produced a higher increase in brain DA than the increase which would be expected by simple summation of the effects of L-DOPA and glaucine and of the glaucine derivatives respectively. At the same time L-DOPA and glaucine, applied together, caused a slighter decrease of brain 5-HT than the decrease produced by the same dose of L-DOPA when the latter was applied alone. It is suggested that the higher increase of brain DA produced by the combination of L-DOPA and the phosphodiesterase inhibitor glaucine or its structural analogues is mainly due to the increased cAMP level.
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PMID:Effects of glaucine and some glaucine derivatives and of their combination with L-DOPA on the brain level of biogenic monoamines. 718 77

A putative 5-HT4 receptor-mediated depolarization of the rat isolated vagus nerve has been studied using a grease-gap extracellular recording technique. Ondansetron (1 microM) was used to block the predominant 5-HT3 receptor mediated depolarization in this preparation and the effects of the 5-HT4 receptor antagonists DAU 6285 (endo-8-methyl-8-azabicyclo [3.2.1] oct-3-yl-2,3-dihydro-6-methoxy-2-oxo-1H-benzimidazole-1- carboxylate HCl); 0.3, 1.0 or 3.0 microM and SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)-ethyl ester HCl); 0.1, 0.3 or 1.0 microM were studied on the residual, ondansetron-resistant, component of the response. The effects of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) and of forskolin on the ondansetron-resistant response were also studied. Both DAU 6285 and SDZ 205-557 acted as competitive antagonists of the ondansetron-resistant response to 5-HT with pA2 values of 6.8 (6.7-7.1, n = 12) and 7.1 (6.9-7.5, n = 12) respectively. The vagus nerve was depolarized by IBMX (100 microM) or forskolin (10 microM), the effects being similar to the maximum response to 5-HT. In the presence of IBMX (100 microM) or forskolin (10 microM) the ondansetron-resistant component of the response to 5-HT was enhanced and the 5-HT3 receptor-mediated component reduced. These results with DAU 6285 and SDZ 205-557 are consistent with a 5-HT4 receptor-mediated mechanism of the ondansetron-resistant depolarizing response to 5-HT.
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PMID:Further characterization of the putative 5-HT4 receptor mediating depolarization of the rat isolated vagus nerve. 747 28

5-Hydroxytryptamine (5-HT) is present in nerve fibres descending from the brainstem Raphe nuclei to motoneurones and its release is thought to exert excitatory actions. 5-HT, applied from the outside, directly depolarizes spinal and cranial motoneurones in slices. This action of 5-HT is mediated, in part, by an inwardly rectifying cationic current, Ih. In cardiac cells, an equivalent current, if, has been shown to be directly activated by adenosine 3':5'-cyclic monophosphate (cAMP) applied to the inside of the patch membrane. By applying the whole-cell method to thin slices of brainstem and spinal cord, we have shown that intracellularly applied camp and extracellularly applied dibutyryl camp or forskolin mimics the inward current induced by 5-ht. The selective cAMP phosphodiesterase inhibitor, Ro 20-1724, clearly prolonged the 5-HT-induced current. Maximal doses of dibutyryl cAMP or forskolin occluded the 5-HT-induced current. The broad spectrum protein kinase inhibitors 1-(5-isoquinolinesulphonyl)-2-methlypiperazine (H-7) and N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) had no effect on the currents induced by 5-HT and forskolin. From these results, we suggest that activation of 5-HT receptors on the motoneuronal membrane stimulates formation of intracellular cAMP, thereby inducing the inward current, possibly by a direct action on Ih.
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PMID:Adenosine 3':5'-cyclic monophosphate mediates a 5-hydroxytryptamine-induced response in neonatal rat motoneurones. 747 31

The present study was aimed at investigating the effect of substance P (SP) on the contractile activity of isolated antral muscle strips of rat and its underlying mechanism. Isolated strips were incubated in an organ bath into which SP was added with or without pretreatment of some antagonists or inhibitors. The results were as follows: (1) SP increased the contractile amplitude of the strips in a dose-dependent manner from 8 x 10(-11) to 8 x 10(-7) mol. At 4 x 10(-8) mol the amplitude was increased by 160.9 +/- 23.0%, while the automaticity of the strips was not affected. (2) This effect of SP could be partially inhibited by hexamethonium (ganglionic blocker), cyproheptadine (blocker of 5-HT2 receptor), diphenhydramine (blocker of H1 receptor), or aminophylline (inhibitor of phosphodiesterase), but not by atropine, propranolol, phentolamine, haloperidol, or naloxone. These results suggested that SP might be a non-cholinergic excitatory transmitter. Its spasmogenic action might be mediated by activating 5-HT neurons, which elicited release of histamine or directly acted on muscle cells.
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PMID:[Effect and its mechanism of substance P on contractile activity of isolated antral muscle strips of rat]. 752 70

1. The effects of the putative endogenous neuromodulator serotonin (5-HT) on the fast extensor and flexor tibiae motor neurons in the locust (Schistocerca gregaria) metathoracic ganglion, were analyzed. 2. 5-HT consistently increased the duration of the fast extensor spike and usually reduced the afterhyperpolarization, although this effect was less consistent. The spike broadening in the fast extensor was associated with an increase in the amplitude of the excitatory postsynaptic potential (EPSP) evoked monosynaptically in the flexor motor neurons by fast extensor stimulation. 5-HT also increased the membrane resistance of the fast extensor and flexor tibiae motor neurons. 3. The effects of 5-HT were mimicked by bath application of the 5-HT uptake inhibitor imipramine, and blocked by the 5-HT receptor antagonist ketanserin. The effects were also mimicked by dibutryl cyclic AMP, a membrane permeant analogue of cyclic AMP, and by the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine, but not by dibutryl cyclic GMP. The 5-HT-dependent modulation was blocked by the protein kinase A inhibitor H8. In addition, injection of cyclic AMP into the fast extensor or a flexor motor neuron could mimic the effects of 5-HT on these neurons. 4. 5-HT probably broadened the FETi action potential by modulating potassium conductances responsible for spike repolarization. 5. These results show that 5-HT modulates both the fast extensor and flexor tibiae motor neurons, resulting in potentiation of synaptic transmission between these neurons. In addition, the increase in flexor membrane resistance will potentiate other inputs onto these cells, which will affect the output of the motor neurons during locomotion.
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PMID:Serotonergic modulation of locust motor neurons. 754 32

1. We studied the roles of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-gated Na+ current (INa,cAMP) in the serotonin (5-HT)-induced excitation of putatively serotonergic "G" neurons of the pedal ganglion of Pleurobranchaea californica. Currents were recorded under voltage clamp during 5-HT application and iontophoretic intracellular cAMP injections. INa,cAMP responses to pulsed injections of cAMP were occluded by 5-HT-induced inward current (I5-HT). Occlusion was qualitatively and quantitatively similar to that observed during steady-state activation of INa,cAMP by tonic iontophoretic injection of cAMP. 2. Those neurons exhibiting occlusion of INa,cAMP during 5-HT application also exhibited depolarization-induced (Ca(2+)-dependent) inactivation of both INa,cAMP and I5-HT. The magnitudes of the inactivation to depolarizing pulses of I5-HT or INa,cAMP were similar. Recoveries from inactivation for I5-HT and INa,cAMP followed similar exponentially decaying time courses. 3. The decay rate of the INa,cAMP response is affected by phosphodiesterase inhibitors and can be taken as a sensitive measure of the rate of cAMP degradation. As background steady-state INa,cAMP was increased by larger tonic cAMP injections, the decay rate of super-imposed INa,cAMP responses to pulsed injections of cAMP was slowed as would be expected from saturation of endogenous phosphodiesterase activity. The decay of INa,cAMP responses to pulsed cAMP injections superimposed on I5-HT were similarly slowed, suggesting that 5-HT action is mediated specifically by cAMP. 4. The decay rate constants for INa,cAMP responses to pulsed injections of cAMP superimposed on I5-HT did not differ from those of INa,cAMP responses superimposed on equivalent, background steady-state INa,cAMP induced by tonic injection of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP-gated sodium current in neurons of the pedal ganglion of Pleurobranchaea californica is activated by serotonin. 766 35

1. Serotonin (5-HT) reduced the after-hyperpolarization (AHP) amplitude in tactile sensory neurones (T) but not in pressor (P) or nociceptive (N) cells of the leech. 2. Adenylate cyclase activators, phosphodiesterase inhibitors and membrane permeant analogues of cyclic adenosine monophosphate (cyclic AMP) mimicked the effect of 5-HT in reducing the AHP amplitude in T neurones. 3. Ionophoretic injection of cyclic AMP in T cells reduced the AHP amplitude, while cyclic guanosine monophosphate (cyclic GMP) or adenosine-5'-monophosphate (AMP) were without effect. 4. Inhibition of adenylate cyclase by the drug RMI 12330A (also known as MDL 12330A) suggested that 5-HT reduced the AHP amplitude through cyclic AMP. 5. 8-Bromoadenosine-3'-5'-cyclic monophosphate (8-Br-cyclic AMP) was still able to reduce the AHP amplitude after blocking the Ca(2+)-activated K+ conductance with CdCl2 and converted the normal hyperpolarization which follows the intracellular injection of Na+ into a depolarization. In addition, the cyclic AMP analogue slowed down and reduced the repolarization usually induced by CsCl after perfusion with K(+)-free solution. It is proposed that, in T sensory neurones, cyclic AMP mediates the inhibition of the Na(+)-K+ electrogenic pump induced by 5-HT application.
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PMID:Cyclic AMP mediates inhibition of the Na(+)-K+ electrogenic pump by serotonin in tactile sensory neurones of the leech. 768 93

The influence of internal Ca2+ ions has been investigated during intracellular perfusion of isolated neurones from pedal ganglia of Helix pomatia in which serotonin (5-HT) induces a cyclic-adenosine-monophosphate-(cAMP)-dependent enhancement of high-threshold Ca2+ current (ICa). Internal free Ca2+ ([Ca2+]i) was varied between 0.01 and 10 microM by addition of Ca(2+)-EGTA [ethylenebis(oxonitrilo)tetraacetate] buffer. Elevation of [Ca2+]i depressed the 5-HT effect. The dose/effect curve for the Ca2+ blockade had a biphasic character and could be described by the sum of two Langmuir's isotherms for tetramolecular binding with dissociation constants Kd1 = 0.063 microM and Kd2 = 1 microM. Addition of calmodulin (CM) antagonists (50 microM trifluoperazine or 50 microM chlorpromazine), phosphodiesterase (PDE) antagonists [100 microM isobutylmethylxanthine (IBMX) or 5 mM theophylline] and protein phosphatase antagonists [2 microM okadaic acid (OA)] in the perfusion solution caused "anticalcium" action and modified the Ca2+ binding isotherm. Using the effect of OA and IBMX, two components of the total Ca2+ inhibition were separated and evaluated. In the presence of one of these blockers tetramolecular curves with Kd1 = 0.04 microM and Kd2 = 0.69 microM were obtained describing the activation of the retained unblocked enzyme--PDE or calcineurin (CN) correspondingly. The sum of these isotherms gave a biphasic curve similar to that in control. Leupeptin (100 microM), a blocker of Ca(2+)-dependent proteases did not influence the amplitude of 5-HT effect, indicating that channel proteolysis is not involved in the depression. Our findings show that the molecular mechanism of Ca(2+)-induced suppression of the cAMP-dependent upregulation of Ca2+ channels is due to involvement of two Ca(2+)-CM-dependent enzymes: PDE reducing the cAMP level, and CN causing channel dephosphorylation. No other processes are involved in the investigated phenomenon at a Ca2+ concentration of less than or equal to 10 microM.
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PMID:Mechanisms of antagonistic action of internal Ca2+ on serotonin-induced potentiation of Ca2+ currents in Helix neurones. 768 96

The mechanisms by which neurotransmitters regulate neurite extension and growth cone motility have been extensively studied using identified Helisoma neurons regenerating in cell culture. Specific neurons, such as buccal neuron B19, display a complex response to the addition of 5-HT involving the generation of action potentials, influx of extracellular calcium, and cessation of neurite extension and growth cone motility. While several studies have addressed the role of calcium in this cascade, little is known about the mechanism underlying the 5-HT-induced excitation of neuron B19. Therefore, we have begun to characterize the ion currents, receptors, and second messengers involved in the 5-HT-dependent depolarization of B19. Exposure of B19 to 5-HT resulted in the activation of a maintained inward current. Ion substitution experiments revealed that this current was carried mainly by sodium ions. The use of 8-bromo-cAMP, forskolin, or the phosphodiesterase inhibitor isobutyl methylxanthine (IBMX) to increase intracellular cAMP levels all resulted in inward current activation in the absence of 5-HT. Moreover, preloading the neuron with 8-bromo-cAMP was sufficient to prevent further current activation by 5-HT. In addition, the IBMX-activated current was greatly enhanced when induced in the presence of 5-HT. Protein kinase inhibitors failed to prevent 5-HT activation of sodium current, suggesting that cAMP may directly activate the current, independent of phosphorylation. Pharmacological experiments showed the B19 5-HT receptor has an EC50 of approximately 10(-7) M and can be activated by various indole analogs of 5-HT. Furthermore, methysergide displayed partial agonist activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin activation of a cyclic AMP-dependent sodium current in an identified neuron from Helisoma trivolvis. 769 98


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