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)

1 The possibility that cyclic adenosine 3',5'-monophosphate (cyclic AMP) mediates a voltage-dependent inward current elicited by 5-hydroxytryptamine (5-HT) in RB and LB cells of the abdominal ganglion of Aplysia was tested. 2 Intracellular injection of cyclic AMP elicited an inward current with a similar time course, potential dependence and ionic sensitivity as the response to 5-HT. 3 Intracellular injection of guanylyl imidodiphosphate (GMP-PNP), which activated adenylate cyclase, neither mimicked nor enhanced the 5-HT-evoked current. On the contrary, it reduced the current. 4 The phosphodiesterase inhibitors, Ro20-1724, isobutyl methylxanthine (IBMX) and theophylline, each antagonized the voltage-dependent response to 5-HT. To varying degrees they each induced an inward current. 5 The adenylate cyclase antagonist, dithiobisnitrobenzoic acic (DTNB), had no effect on the response to 5-HT when applied either intracellularly or extracellularly. Intracellular injection of the phosphodiesterase activator imidazole also had no effect. 6 Tubocurarine and neostigmine did not reduce the voltage-dependent inward current evoked by 5-HT; methysergide elicited an inward current. 7 Although the observations that cyclic AMP and 5-HT can evoke similar voltage-dependent inward currents in RB and LB neurones of Aplysia might suggest a second messenger role for the cyclic nucleotide, the pharmacological data are inconsistent with this hypothesis.
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PMID:Does cyclic 3' ,5'-adenosine monophosphate act as second messenger in a voltage-dependent response to 5-hydroxytryptamine in Aplysia? 617 22

Stimulation of the branchial or either connective nerve of the abdominal ganglion of Aplysia californica evokes simultaneous responses in cells R15, L8, L9, and L11 which are indistinguishable from those arising from spontaneous interneuron II (INT II) activity. Threshold for the INT II-like response in all cells is identical, suggesting that the response is mediated by INT II activity. The magnitude of the response in each cell increases with stimulus intensity and is subject to both temporal and spatial summation, implying the existence of multiple fibres in each nerve which converge on INT II. Repetitive stimulation evokes long-lasting inhibition in R15. The onset of this phenomenon is always accompanied by an INT II burst in the other follower cells. Long-lasting inhibition in R15 is not accompanied by prolonged INT II activity, suggesting an endogenous mechanism of inhibition. The phosphodiesterase inhibitor, IBMX, potentiates the response of R15 to nerve stimulation without affecting threshold for the response. This is consistent with inhibition by a mechanism endogenous to R15.
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PMID:Long-lasting inhibition of neuron R15 of Aplysia: role of the interneuron II network. 620 9

We have studied the effect of the biogenic amines, serotonin and dopamine, on post-tetanic potentiation (PTP) at an identified synapse in the abdominal ganglion of Aplysia californica. We found that: (1) 10(-7) M perfused serotonin doubles the rate constant of decay of PTP. The effect is specific in that neither the size of the non-potentiated (isolated) EPSP nor the amplitude of PTP is affected. As reported previously, higher doses of serotonin will also increase the amplitude of PTP and decrease the size of the isolated EPSP; (2) 5 X 10(-7) M dopamine in the perfusate increases the rate constant of decay of PTP by about 50%. The effect is also specific in that neither PTP amplitude nor the size of the isolated EPSP is affected; (3) SQ10,631, a serotonin antagonist, blocks the effect of perfused serotonin on PTP decay rate. It does not antagonize the dopamine effect. SQ10,631 also slows the endogenous decay of PTP in some preparations which exhibit an unusually fast PTP decay rate, suggesting a naturally occurring source of serotonin within the ganglion capable of affecting the rate constant of PTP decay; (4) (+)-butaclamol, a dopamine antagonist, blocks the effect of dopamine on the rate constant of PTP decay, whereas (-)-butaclamol has little effect. Butaclamol does not block the effect of serotonin on the rate constant of PTP decay; (5) phosphodiesterase inhibitors potentiate the effect of serotonin on the rate constant of PTP decay, and cyclic AMP analogues mimic the effect of the biogenic amines, suggesting that the aminergic modulation of the rate of decay of PTP is coupled with activation of adenylate cyclase and accumulation of cyclic AMP; and (6) the evidence presented is consistent with the hypothesis that serotonin and dopamine are capable of specifically modifying the rate of change in the efficacy of transmitter release which underlies PTP. It also suggests that the two biogenic amines operate separately and in parallel via presynaptic receptor mechanisms.
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PMID:Separate serotonin and dopamine receptors modulate the duration of post-tetanic potentiation at an Aplysia synapse without affecting other aspects of synaptic transmission. 624 26

Addition of serotonin to the medium bathing an Aplysia abdominal ganglion causes a change in the endogenous bursting activity of the identified neuron R15. At serotonin concentrations in the micromolar range, the predominant effect is an increase in depth and duration of the interburst hyperpolarization and consequent decrease in burst rate. At higher concentrations (10 microM) serototin can inhibit bursting completely. We have shown previously that these changes can be mimicked by bath application or intracellular injection of several cyclic AMP analogs substituted at the 8 position. Voltage clamp analysis indicates that serotonin and cyclic AMP analogs both cause an increase in membrane slope conductance in R15, with reversal potentials for the responses between -75 and -80 mV, close to the K+ equilibrium potential. When the K+ concentration in the bathing medium is changed, the reversal potentials change in a manner suggesting that serotonin and cyclic AMP analogs on K+ conductance are not additive. Furthermore, the effects of low concentrations of serotonin can be potentiated by the phosphodiesterase inhibitor Ro 20-1724. A pharmacological analysis indicates that the serotonin receptor that mediates hyperpolarization in R15 is similar to the serotonin receptor that we have shown to be coupled to adenylate cyclase. The present electrophysiological and pharmacological observations, together with our previous biochemical and pharmacological results, demonstrate that the serotonin-induced hyperpolarization of neuron R15 is mediated by cyclic AMP.
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PMID:Serotonin-induced hyperpolarization of an indentified Aplysia neuron is mediated by cyclic AMP. 625 53

One model of synaptic transmission suggests that transmitters modify postsynaptic permeability through the intermediary of cyclic AMP. Thus, serotonin (5-hydroxytryptamine) evokes in molluscan neurones a decrease in a voltage-dependent K+ conductance which in turn generates a slow inward current when studied in steady voltage-clamp conditions. The serotonin-induced increase of the plateau phase of the spike of an Aplysia sensory neurone can be mimicked by both intracellularly injected cyclic AMP and extracellularly applied phosphodiesterase inhibitors, suggesting that cyclic AMP mediates the effect. We have tested whether a similar mechanism could account for the serotonin slow inward current in identified snail neurones and have found that the intracellular injection of cyclic AMP, but not of cyclic GMP or 5'-AMP, evokes a slow inward current showing similar voltage dependence, inversion potential and ionic properties to the serotonin slow inward current. Phosphodiesterase inhibitors at low concentrations (1-20 microM) potentiate the serotonin slow inward current and at higher concentrations evoke by themselves an inward current, partially or totally occluding the serotonin and cyclic AMP currents. Finally, we have found that in homogenates of pooled identified snail neurones serotonin stimulates the adenylate cyclase, increasing its activity by 50-100%.
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PMID:Role of cyclic AMP in a serotonin-evoked slow inward current in snail neurones. 626 Nov 54

A voltage-dependent inward current is elicited by intracellular application of cyclic AMP in some neurons of Aplysia. The current has a slow time course and is present only at potentials more depolarized than -30 mV. Two other methods of increasing cellular cyclic AMP (phosphodiesterase inhibitors and sodium fluoride activation of adenylate cyclase) also induce an inward current at depolarized potentials.
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PMID:Cyclic AMP induces a voltage-dependent current in neurones of Aplysia californica. 626 81

Multidisciplinary studies of the role of cAMP in synaptic transmission have been made possible by the favorable properties of the molluscan nervous system, and there is now evidence from several laboratories implicating cAMP in physiological responses in various Aplysia nerve and muscle cells (9,10,15,18,21). The results we have obtained satisfy all the criteria (8) necessary to establish that cAMP mediates the response to a neurotransmitter: a) the response is mimicked by intra- or extracellular application of cAMP derivatives, and by activation of adenylate cyclase within R15; b) a phosphodiesterase inhibitor enhances the response to low concentrations of serotonin; c) serotonin causes cAMP to accumulate within R15, and stimulates adenylate cyclase activity in membranes prepared from R15 cell bodies; and d) the serotonin receptors mediating adenylate cyclase stimulation and R15 hyperpolarization are pharmacologically very similar. This is the first time all these criteria have been satisfied in a neuronal system, and thus we conclude that the serotonin-induced increase in potassium conductance in neuron R15 is mediated by cAMP.
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PMID:Cyclic AMP modulation of a specific ion channel in an identified nerve cell: possible role for protein phosphorylation. 626 5

Serotonin (5-hydroxytryptamine, 5-HT) shifts the phase of the circadian rhythm in the eye of Aplysia. We have examined the role of cAMP in mediating the effects of 5-HT on the rhythm. The phase shifts produced by 5-HT are mimicked by treatments that should increase intracellular levels of cAMP. An analogue of cAMP-8-benzylthio-cAMP, advanced and delayed the rhythm at phases in which 5-HT had similar effects on the rhythm. In addition, two phosphodiesterase inhibitors, Ro-20-1724 and papaverine, caused advance phase shifts where 5-HT advances the rhythm. The phosphodiesterase inhibitors Ro-20-1724 and 3-isobutyl-1-methylxanthine each potentiated the effect of subthreshold doses of 5-HT on the rhythm. The effects of 5-HT and 8-benzylthio-cAMP on the rhythm were nonadditive, indicating that 5-HT and 8-benzylthio-cAMP affect the rhythm through a common pathway. Finally, 5-HT produced large changes (13-fold) in the levels of cAMP in the eye. These results indicate that cAMP mediates the effect of 5-HT on the rhythm. There are two possible roles for cAMP in the circadian system. Either the cAMP system is an intracellular step in an entrainment pathway or it is part of the biological clock. Because 5-HT, 8-benzylthio-cAMP, and three phosphodiesterase inhibitors inhibit impulses from the eye, cAMP may also mediate the inhibition produced by 5-HT, or it might be involved in regulating the frequency of spontaneous impulses throughout the day.
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PMID:Mechanism for shifting the phase of a circadian rhythm by serotonin: involvement of cAMP. 628 77

The effect on the Ca-dependent potassium current, IK(Ca), of procedures that increase intracellular cAMP levels was studied in Aplysia neurons using three different pharmacological approaches. Exposure to cAMP analogues which were either resistant to or protected from phosphodiesterase hydrolysis caused an increase in IK(Ca) from 30 to 50% in 10 min. The degree of reversibility of this effect varied from complete with db cAMP to very little with pcpt cAMP. Exposure to cholera toxin, which stimulates the synthesis of endogenous cAMP, increased IK(Ca) 25% in 10 min and the effect was not reversible. Both approaches were effective in all seven neuron types studied. Application of serotonin plus phosphodiesterase inhibitor caused an increase in IK(Ca) in neuron R15 but not in the other neuron types. Application of pentylene tetrazole (PTZ) led to a decrease in IK(Ca). It is proposed that elevation of cyclic AMP mediates an increased sensitivity of the IK(Ca) channel to Ca ions.
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PMID:Cyclic AMP enhances calcium-dependent potassium current in Aplysia neurons. 632 11

The effects of bath-applied sodium nitroprusside (SNP), a nitric oxide (NO) donor, on an acetylcholine ACh-induced K+ current recorded from identified neurons (R9 and R10) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques. Bath-applied SNP (25-50 microM) reduced the ACh-induced K+ current in the neurons without affecting the resting membrane conductance and holding current. The suppressing effects of SNP on the current were completely reversible. Intracellular injection of 1 mM guanosine 3',5'-cyclic monophosphate (cGMP) or bath-applied 50 microM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase (PDE) inhibitor, also inhibited the ACh-induced current, thus mimicking the effect of the NO donor on the ACh-induced current. In contrast, pretreatment with methylene blue (10 microM), an inhibitor of guanylate cyclase, and hemoglobin (50 microM), a nitric oxide scavenger, decreased the SNP-induced inhibition of the ACh-induced current. These results suggest that SNP, a NO donor, inhibits the ACh-induced K+ current, and that the mechanism of NO inhibition of the ACh-induced current recorded from identified Aplysia neurons involves cGMP-dependent protein kinase.
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PMID:Nitric oxide donor sodium nitroprusside inhibits the acetylcholine-induced K+ current in identified Aplysia neurons. 892 26


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