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

Activation of a physiological response by the adenylate cyclase activator, forskolin, has been suggested as a new criterion for testing the role of cyclic AMP. In Aplysia, motoneurone B16, which innervates muscle 15, is activated by the peptide egg-laying hormone (ELH). In high magnesium-low calcium medium, used to block synaptic activity, forskolin produced a similar response to ELH. Forskolin, at a concentration of 100 microM, consistently activated the ELH-sensitive neurone; vehicle produced no response while 30 microM forskolin usually produced lower levels of activity than 100 microM. The data are consistent with cyclic AMP mediation of the ELH response.
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PMID:Forskolin activation of an identified peptide-sensitive motoneurone in Aplysia. 631 17

An adenylate cyclase inhibitor, RMI 12330A, is able to depress cAMP synthesis stimulated by serotonin in the abdominal ganglion of Aplysia depilans and punctata. This substance reversibly blocked the heterosynaptic facilitation, induced by activation of serotonergic pathways, of the EPSP recorded from L7 motoneuron in abdominal ganglion after electrical stimulation of the siphon nerve. RMI 12330A, injected into whole unrestrained animals, inhibited the short-term dishabituation of the siphon withdrawal reflex. These findings demonstrate that the increase of endogenous cAMP in the sensory neurons mediating the gill and siphon withdrawal reflex is an essential step in the mechanism of potentiation of the transmitter output underlying heterosynaptic facilitation and short-term behavioral sensitization.
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PMID:Heterosynaptic facilitation and behavioral sensitization are inhibited by lowering endogenous cAMP in Aplysia. 631 91

The effects of the adenylate cyclase inhibitor GDP beta S on the response of Aplysia neuron R15 to serotonin (5HT) were investigated. Previous studies have demonstrated that 5HT causes an increase in K+ conductance in R15 and that the response is mediated by cAMP. At concentrations in the micromolar range, GDP beta S inhibits the stimulation of adenylate cyclase by 5HT in particulate fractions from Aplysia ganglia. When micromolar concentrations of GDP beta S are injected into neuron R15, there is no effect on the resting membrane conductance, but the increase in K+ conductance normally elicited by 5HT is completely inhibited. Furthermore, the decrease in inward current normally elicited by dopamine (DA), which does not appear to involve cAMP, is not affected by micromolar concentrations of GDP beta S. In addition, application of 8-benzylthio cAMP to R15 can evoke an increase in K+ conductance even after the injection of GDP beta S, which indicates that events subsequent to the activation of adenylate cyclase are not inhibited by the GDP analogue. In contrast, when millimolar concentrations of GDP beta S are injected into R15, direct effects on membrane conductance are observed and the response of R15 to 5HT is enhanced. Although these effects of high concentrations of GDP beta S are only poorly understood, the results with micromolar concentrations are consistent with the hypothesis that stimulation of adenylate cyclase is necessary for the 5HT-induced increase in K+ conductance in neuron R15.
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PMID:Intracellular injection of guanyl nucleotides alters the serotonin-induced increase in potassium conductance in Aplysia neuron R15. 632 83

The effects of FMRFamide (Phe-Met-Arg-Phe-NH2), YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2), and Met-enkephalin (Tyr-Gly-Gly-Phe-Met) on the isolated Aplysia anterior gizzard were examined. (i) FMRFamide inhibits spontaneous gut activity. While YGG-FMRFamide also inhibits spontaneous activity it is less potent than FMRFamide. Met-enkephalin does not affect spontaneous gut activity. (ii) FMRFamide inhibits the excitatory response of acetylcholine on both the anterior gizzard of Aplysia and the isolated stomach region of Navanax. (iii) Neither FMRFamide, YGG-FMRFamide, Met-enkephalin, nor acetylcholine stimulated the activity of adenylate cyclase in the Aplysia anterior gizzard.
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PMID:FMRFamide effects on spontaneous and induced contractions of the anterior gizzard in Aplysia. 662 35

A brief train of electrical stimuli to the pleuroabdominal connective of Aplysia produces a cumulative depolarization in the peptidergic bag cell neurons within the abdominal ganglion. This response is followed by an afterdischarge which lasts for about 30 min, and then by a prolonged refractory period lasting for several hours. During the refractory period the cumulative depolarization in response to stimulation is attenuated, and stimulation either fails to initiate afterdischarges or produces discharges of much shorter duration. We have used the cationophore X537A to test the hypothesis that the prolonged refractory period is caused by calcium entry into the bag cell neurons during the afterdischarge. Exposure of intact bag cell clusters to X537A at concentrations from 1 to 10 microM for a period of 20 min in calcium-containing media produced no change in their resting potentials or in their ability to generate action potentials, but induced a state resembling natural refractoriness in response to subsequent stimulation. Both natural refractoriness and that induced by X537A could be overcome by extracellular tetraethylammonium ions (90 mM). Dose response data showed that concentrations of ionophore of 2.5 to 5.0 microM produce an attenuation of afterdischarge that is similar to that following a stimulated afterdischarge. These concentrations of X537A also produced an enhancement of 3H-labeled peptide release from these cells that is comparable to that observed on stimulation of an afterdischarge. Moreover, the time course of recovery from exposure to 5.0 microM X537A parallels that of natural refractoriness, recovery being essentially complete about 20 hr after X537A exposure or stimulation. The ionophore did not affect the mean duration of afterdischarge when applied in calcium-deficient media. The electrical effects of X537A were investigated using isolated bag cell neurons in cell culture. After treatment with the adenylate cyclase activator, forskolin, and theophylline, such isolated cells show many of the electrical changes occurring in intact bag cell clusters at the onset of afterdischarge, including the enhancement of action potentials, as well as increased input resistance and the emergence of oscillations in membrane potential. None of these parameters was significantly affected by concentrations of ionophore that induce refractoriness. In response to repetitive intracellular stimulation, however, some forskolin-treated cells undergo a cumulative depolarization which is similar to that seen at the onset of afterdischarge in intact clusters. This cumulative depolarization was found to be attenuated or abolished by 5.0 microM X537A.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium entry causes a prolonged refractory period in peptidergic neurons of Aplysia. 663 77

The distribution of receptors for serotonin and dopamine has been studied in various neuronal and non-neuronal tissues from Aplysia californica using: (1) a [3H]LSD binding assay; and (2) stimulation of adenylate cyclase activity. High levels of specific [3H]LSD binding were found in all ganglia and nerves examined. Lower levels of binding were present in a number of muscle tissues and in the sheath surrounding the central ganglia. The ability of serotonin and dopamine to inhibit [3H]LSD binding depended upon the tissue examined. In muscle tissue, most of the binding was sensitive to serotonin. In contrast, a number of ganglia (e.g. the pleural, abdominal or cerebral) contained a considerable proportion of dopamine-sensitive binding. A limited pharmacological analysis of serotonin-sensitive [3H]LSD binding indicated that Aplysia serotonin receptors are closely related to those found in the snail, Helix pomatia, and in rat brain. Adenylate cyclase activity in membranes from Aplysia ganglia, muscles and connective nerves was stimulated by serotonin (but not by dopamine). The amount of serotonin-sensitive adenylate cyclase correlated well with the amount of serotonin-sensitive [3H]LSD binding in most tissues. D-LSD was a partial agonist on the serotonin-sensitive adenylate cyclase, whereas the pharmacologically inactive stereoisomer L-LSD was without effect. The high density of serotonin receptors in pleuro-abdominal connective nerves, and their presence in the connective tissue sheaths surrounding the ganglia, suggests that not all of these receptors are located at synapses. On the other hand, the tissue distribution of dopamine and serotonin receptors, as measured by these techniques, is consistent with that expected from electrophysiological data.
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PMID:Distribution of serotonin and dopamine receptors in Aplysia tissues: analysis by [3H]LSD binding and adenylate cyclase stimulation. 735 15

The bag cell peptides (alpha-, beta-, and gamma-BCP) are secreted by the neuroendocrine bag cells of Aplysia, and provide feedback modulation of bag cell excitability and cAMP levels. We report here that if 200-500 mM NaCl is included in the assay buffer, the BCPs alter adenylate cyclase activity in a manner consistent with their effects on cAMP levels in intact bag cells. Specifically, beta-BCP and the related peptide A from the atrial gland stimulate the enzyme, while the effects of alpha-BCP(1-7) and gamma-BCP are temperature-dependent, stimulating at 30 degrees C and inhibiting at 15 degrees C. Both stimulation and inhibition require GTP, suggesting mediation by Gs and Gi. The ionic requirements of stimulation and inhibition differ: Cl- is necessary to support stimulation, but not inhibition. Moreover, pertussis toxin blocks inhibition, but does not affect stimulation. These results suggest that the temperature-sensitive mechanism lies upstream from the G-proteins in the signal transduction pathway.
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PMID:Temperature-dependent stimulation and inhibition of adenylate cyclase by Aplysia bag cell peptides. 838 57

Recent experiments indicate that the calcium store (e.g., endoplasmic reticulum) is involved in electrical bursting and [Ca2+]i oscillation in bursting neuronal cells. In this paper, we formulate a mathematical model for bursting neurons, which includes Ca2+ in the intracellular Ca2+ stores and a voltage-independent calcium channel (VICC). This VICC is activated by a depletion of Ca2+ concentration in the store, [Ca2+]cs. In this model, [Ca2+]cs oscillates slowly, and this slow dynamic in turn gives rise to electrical bursting. The newly formulated model thus is radically different from existing models of bursting excitable cells, whose mechanism owes its origin to the ion channels in the plasma membrane and the [Ca2+]i dynamics. In addition, this model is capable of providing answers to some puzzling phenomena, which the previous models could not (e.g., why cAMP, glucagon, and caffeine have ability to change the burst periodicity). Using mag-fura-2 fluorescent dyes, it would be interesting to verify the prediction of the model that (1) [Ca2+]cs oscillates in bursting neurons such as Aplysia neuron and (2) the neurotransmitters and hormones that affect the adenylate cyclase pathway can influence this oscillation.
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PMID:Modeling slowly bursting neurons via calcium store and voltage-independent calcium current. 869 30

Serotonin (5-HT) is involved in the control of various behaviors in Aplysia californica, including reproduction, feeding, locomotion, circadian rhythm, synaptic plasticity, and synaptic growth. The large variety of functions of 5-HT is mediated by different receptor subtypes that are coupled to different second-messenger systems. Here, we report the cloning of a cDNA coding for an Aplysia G-protein-coupled 5-HT receptor (5-HTap1). Its deduced amino acid sequence resembles those of the 5-HT1 receptor subfamily. When expressed in stable cell lines, 5-HTap1 exhibits high-affinity binding for the serotonergic radioligand [N-methyl-3H]lysergic acid diethylamide. This binding is competed by several 5-HT agonists and antagonists, and the pharmacological profile of inhibition has some similarities with those of 5-HT1 and 5-HT7 receptors. Application of 5-HT or its agonists 5-carboxamidotryptamine maleate and (+/-)-8-hydroxy-2-(di-n-propyl-amino) tetralin hydrobromide on cells transformed with 5-HTap1 produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation. 5-HTap1 is thus negatively coupled to adenylate cyclase. The production of antiserum against the 5-HTap1 receptor allowed us to examine its expression in animal tissues. The receptor protein is detected in every tissue examined, although it seems only weakly expressed in some samples. The receptor is also found in every ganglia of the nervous system, both in the sheath and in the neurons. 5-HTap1 mRNA is absent from the sheath, indicating that the protein observed there is probably located on the nerve terminals.
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PMID:Cloning and functional expression of an Aplysia 5-HT receptor negatively coupled to adenylate cyclase. 967 50

Serotonin has been shown to be a neuromodulator in the Aplysia californica CNS. The diversity of serotonin actions is due to the existence of several different receptor subtypes. In this study we report the cloning of a full-length cDNA, coding for a novel serotonin receptor (5-HTap2). The receptor protein bears the characteristics of G protein-coupled receptors. It shares 68% and 34% of its amino acid sequence identity with the 5-HTlym receptor from Lymnaea stagnalis and the mammalian 5-HT1A receptor, respectively. When transfected in HEK 293 cells, 5-HTap2 was negatively coupled to adenylate cyclase. Ligand binding analysis indicated that the order of potencies of various drugs for the inhibition of [3H]LSD binding was: methiothepin > metergoline > 5-CT > PAPP > 5-HT > ketanserin > NAN-190 > 8-OH-DPAT > clozapine. RT-PCR amplification of RNA isolated from different tissues indicated that this receptor is expressed in the CNS and in bag cells. The expression of 5-HTap2 restricted to the CNS suggests an important role for this receptor in the modulation of neuronal functions in Aplysia. Moreover, the high expression of 5-HTap2 in the bag cells, associated with its pharmacological profile, suggests that this receptor may be implicated in modulating the afterdischarge during the egg-laying behavior.
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PMID:Functional characterization of a novel serotonin receptor (5-HTap2) expressed in the CNS of Aplysia californica. 1190 24


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