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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octopamine is highly concentrated in neurones of several invertebrate species. Unlike in mammals, octopaminergic neurones in invertebrates are spatially separated from catecholaminergic neurons. In identified nerve cells of Aplysia, however, this amine coexists with other putative neurotransmitters. Octopamine is synthesized in nerves from tyrosine and tyramine and metabolised mainly by monoamine oxidase. When lobster nerves are depolarized, octopamine is liberated by a Ca2+-dependent process. A specific adenylate cyclase is stimulated by octopamine in several invertebrates to activate phosphorylase in the cockroach, induce a light-flash in firefly lattern or inhibit rhythm contractions in locust muscle. All of these observations provide compelling evidence that octopamine is a neurotransmitter in invertebrates. In mammals octopamine is localised in nerves in peripheral tissues and brain where it seems to coexist with noradrenaline, the catecholamine being present in much higher concentrations. Octopamine is released from nerves together with noradrenaline and it may under certain conditions modify the actions of the adrenergic neurotransmitter. Octopamine is present in unusually high concentrations in certain neurological and hepatic diseases and may have a pathophysiological role.
...
PMID:Octopamine. 1 10

Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.
...
PMID:Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica. 2 27

1. Heterosynaptic facilitation (modification of synaptic transmission by a neuron influencing the terminals of the presynaptic neuron) was studied in the pleural ganglion of Aplysia. Among several identified synapses, heterosynaptic facilitation was observed only in one type (EIPSP synapses) when repetitive stimulation was applied to the tentacular nerve or to a particular identified neuron. 2. Serotonin was shown to increase the amplitude of the EIPSP at this synapse; this facilitatory effect was prolonged in the presence of theophylline and mimicked by cyclic AMP. 3. When transmission was abolished by calcium-free solution, calcium injected in the region of the synapse caused partial recovery of the EIPSP; when calcium injection was preceded by serotonin injection near the same terminal, the EIPSP was much larger than with calcium injection alone. 4. It was concluded that the activation of one neuron (the heterosynaptic neuron) caused it to release serotonin, which activated an adenylate cyclase in the pre-synaptic terminals of another neuron. Consequent accumulation of cyclic AMP in these terminals is supposed to have increased their voltage-dependent calcium conductance and hence the amount of transmitter released during an action potential.
...
PMID:The role of cyclic AMP in the modulation of synaptic efficacy. 3 32

The phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) inhibitor thepohylline enhances both the amplitude and duration of a long-lasting synaptic hyperpolarization in identified neuron R15 in Aplysia californica. Intraneuronal injection into R15 of glanylyl-imidodiphosphate, an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activator, results in a deep and long-lasting hyperpolarization of the cell, similar to that produced by synaptic stimulation. Biochemical analysis confirms that guanylyl-imidodiphosphate activates adenylate cyclase in Aplysia californica nervous tissue, without affecting phosphodiesterase activity. These observations suggest that adenosine 3':5'-cyclic monophosphate plays a role in long-lasting synaptic inhibition and are consistent with a post-synaptic site of action for adenosine 3':5'-cyclic monophosphate.
...
PMID:Intraneuronal guanylyl-imidodiphosphate injection mimics long-term synaptic hyperpolarization in Aplysia. 18 52

The neuroendocrine bag cells in the abdominal ganglion of Aplysia generate a long-lasting synchronous afterdischarge upon brief stimulation of an afferent pathway. After this afterdischarge the cells become refractory to further synaptic stimulation. We find that synchrony, afterdischarge, and prolonged refractoriness are properties that can be expressed in the isolated asomatic neurites of the bag cells. We have distinguished two independent types of refractoriness. The first (type I) is seen as a failure of action potentials generated in the tips of bag cell neurites to invade cell somata. The second form of refractoriness (type II) controls the duration of afterdischarge such that stimuli after the first afterdischarge produce only very short afterdischarges or fail to elicit an afterdischarge. Type II refractoriness is sensitive to serotonin and certain of its analogues, and to dopamine and the methylxanthine phosphodiesterase inhibitors. Extracellularly applied serotonin suppresses an ongoing afterdischarge while dopamine and the phosphodiesterase inhibitors, when applied at the end of the first afterdischarge, generate a subsequent afterdischarge of long duration without further electrical stimulation. None of these compounds influenced the degree of type I refractoriness. We have shown that both serotonin and dopamine stimulate the formation of cyclic AMP in the bag cell clusters and in the pleurovisceral connectives and that the occurrence of an afterdischarge is associated with a specific increase in total cyclic AMP in bag cell bodies. Moreover, afterdischarges can be generated in unstimulated preparations by extracellular application of the cyclic AMP analogues, 8-benzylthio-cyclic AMP or 8-methylthio-cyclic AMP. Our data suggest that serotonin and/or dopamine may control bag cell activity and that activation of adenylate cyclase is linked to bag cell afterdischarge.
...
PMID:Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites. 21 16

Application of FMRFamide (Phe-Met-Arg-Phe-NH2) induced a slow depolarization in neurons of the Aplysia abdominal ganglion. In voltage-clamped cells, FMRFamide induced a slow inward current that increased when the membrane was depolarized beyond -85 mV, showing a negative slope conductance. However, this inward current never reversed to outward current when hyperpolarized beyond the equilibrium potential for K+. The FMRFamide-induced response was markedly augmented in Ca(2+)-free media, but depressed in Na(+)-free media. It was unaffected by a change in external potassium. Intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) significantly depressed the FMRFamide response in a dose-dependent way. Injection of cholera toxin (CTX) which did not cause any current response, selectively and irreversibly blocked the FMRFamide response. Neither 3'-deoxyadenosine, an inhibitor of adenylate cyclase, nor H-8, an inhibitor of cyclic adenosine 3',5'-monophosphate (cyclic AMP)-dependent kinase, depressed the FMRFamide response. 3-Isobutyl-1-methylxanthine (IBMX) did not augment the FMRFamide response appreciably. The FMRFamide response was not occluded at all by a relatively large injection of 8-bromo-cyclic AMP. It was concluded that the FMRFamide response is produced by the opening of the voltage-dependent Na(+)-channels via activation of a certain CTX-sensitive G-protein which is different from conventional "Gs" that activates adenylate cyclase.
...
PMID:G-protein mediating the slow depolarization induced by FMRFamide in the ganglion cells of Aplysia. 128 79

A mathematical model, called the Learning Gate Model (LGM), that describes phenomena responsible for biological synaptic plasticity, is presented. The functionality of the model are mainly based on the work of Kandel and colleagues on the most elementary forms of learning observed in the Aplysia Californica marine mollusc. In particular, emphasis is placed on the double temporal dynamics of synaptic plasticity and the temporal specificity of classical conditioning. By properly modeling the effect of the binding of Ca++ ions to the serotonin-sensitive adenylate cyclase enzyme, it is shown how a positively accelerated learning curve can be obtained for sensitization and classical conditioning. Phenomena of spontaneous recovery and second-order conditioning are reproduced through simulations. Mathematical analyses of the temporal trace of conditioned stimulus and of the Short-Term Memory steady state are also given.
...
PMID:An analytical short- and long-term memory model of presynaptic plasticity. 151 12

Activity-dependent facilitation is a mechanism of associative synaptic plasticity that contributes to classical conditioning in Aplysia. Previous studies of activity-dependent facilitation in the mechanosensory neurons of Aplysia suggested that the Ca2+ influx during paired spike activity enhances the transmitter-stimulated, cAMP-dependent, presynaptic facilitation in these cells. Moreover, paired activity was found to potentiate the activation of the adenylate cyclase by transmitter. It was therefore proposed that the Ca2+/calmodulin-sensitive cyclase may serve as a site of interaction between the inputs from the conditioned and unconditioned stimuli. These studies were carried out to test whether a Ca2+/calmodulin-sensitive adenylate cyclase in the Aplysia CNS has the properties necessary to mediate such an associative interaction. Three lines of evidence indicate that the same cyclase molecules that are sensitive to Ca2+/calmodulin are also stimulated by receptor to facilitatory transmitter via the stimulatory G-protein, Gs: First, calmodulin inhibitors reduced stimulation of the cyclase by facilitatory transmitter. When membranes had been preexposed to one of these inhibitors, trifluoperazine, the addition of exogenous calmodulin partially reversed the inhibition. Second, when Gs had been activated by GTP gamma S, so that it persistently activated the catalytic unit of the cyclase, stimulation of the cyclase by Ca2+ was greatly amplified, suggesting that the two inputs interact in activating a common population of the enzyme. Third, solubilized cyclase activity that bound to calmodulin-Sepharose in a Ca(2+)-dependent manner was stimulated by Gs, which had been partially purified from Aplysia CNS, as well as by Ca2+/calmodulin. Having demonstrated dual activation of the cyclase, we have explored the dependence of cyclase activation on the temporal pattern of Ca2+ and transmitter addition. Optimal activation required that a pulse of Ca2+ temporally overlap the addition of facilitatory transmitter. These several results suggested that the dually regulated adenylate cyclase might underlie the temporal requirements for effective classical conditioning in this system.
...
PMID:Biochemical studies of stimulus convergence during classical conditioning in Aplysia: dual regulation of adenylate cyclase by Ca2+/calmodulin and transmitter. 167 20

alpha-Bag cell peptide (alpha-BCP), one of the secretory products of the neuroendocrine bag cells in Aplysia, has been reported by various investigators to have either excitatory or inhibitory feedback effects. Though conflicting, these results may be explained by the difference in temperature at which the experiments were performed. Because egg laying in this animal is temperature dependent, the alteration in function of this peptide by temperature may offer a possible molecular basis for the seasonal regulation of egg laying. This hypothesis was investigated by assessing the feedback actions of alpha-BCP at various temperatures. At 15 degrees C, alpha-BCP hyperpolarized bag cells, shortened the duration of synaptically evoked bag cell discharges, and reduced the number of action potentials per discharge. However, at 20 degrees C, the peptide depolarized bag cells, lengthened discharges, and increased the number of action potentials per discharge. A temperature-dependent influence on bag cell cAMP levels may underlie these effects, because alpha-BCP reduced basal cAMP levels in intact bag cells at temperatures of 15 degrees C and below, while at 17-22 degrees C it increased these levels. However, the inhibitory effects of alpha-BCP on stimulated adenylate cyclase activity in bag cell homogenates were not temperature dependent. Moreover, a low-Ca2+/high-Mg2+ solution abolished alpha-BCP's ability to increase bag cell cAMP levels at 20 degrees C. This suggests that the peptide may evoke the secretion of an excitatory modulator at the higher temperature. These results imply that alpha-BCP is autoinhibitory at typical winter temperatures, but becomes autoexcitatory as ocean temperature rises in the summer. Thus, the peptide may function in coordination with other factors to regulate egg laying in response to seasonal temperature variations.
...
PMID:Temperature-dependent peptidergic feedback: potential role in seasonal egg laying in Aplysia. 171 Jun 58

Application of 5-hydroxytryptamine (5HT) induces a slowly depolarizing response in the neurons of Aplysia abdominal ganglion. In voltage-clamped cells, 5HT induced a slow inward current that increased steeply with membrane depolarization from -85 mV showing a negative slope conductance, but never reversed into outward when hyperpolarized beyond the equilibrium potential for K+. The 5HT-induced response was markedly augmented in Ca(2+)-free media, but depressed in Na(+)-free media, and unaffected by a change in external potassium. Intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) significantly depressed the 5HT response in a dose-dependent way. Injection of cholera toxin (CTX) selectively blocked the 5HT-induced response, the effect being irreversible. Neither 3'-deoxyadenosine, an inhibitor of adenylate cyclase, nor H-8, an inhibitor of protein kinase A, depressed the 5HT response. 3-Isobutyl-1-methylxanthine (IBMX) did not augment the 5HT response appreciably. The 5HT responses were not depressed at all during a saturated response to Br-cyclic AMP injected intracellularly. It was concluded that the 5HT response is produced by opening of the voltage-dependent Na(+)-channels with activation of CTX-sensitive G-protein but not necessarily with an increase in intracellular cyclic AMP.
...
PMID:A slow voltage-dependent Na(+)-current induced by 5-hydroxytryptamine and the G-protein-coupled activation mechanism in the ganglion cells of Aplysia. 171 63


1 2 3 4 5 6 7 8 Next >>

---