Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nigral basal adenylate cyclase and dopamine-sensitive adenylate cyclase, glutamate decarboxylase, choline acetyltransferase, and tyrosine hydroxylase activities were measured in rats with hemitransections at various levels or with electrolytic lesions of the medial forebrain bundle or the crus cerebri. The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases. The data indicate that the nigral dopamine-sensitive adenylate cylase activity may be localized on neurons afferent to the nigra, probably originating from the globus pallidus and possibly from the tail of the caudate. The results suggest that dopamine, released from nigral dendrites, may influence dopaminergic activity indirectly by modulating impulses transmitted to the nigrostriatal neurons through the crus cerebri.
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PMID:Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum. 1 59

The dopamine (DA)-sensitive adenylate cyclase in the substantia nigra was assayed in rats which had been subjected to 3 different kinds of brain lesion: (1) unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle; (2) unilateral lesions of the descending strio-nigral and pallido-nigral projections; (3) total lesions of the serotoninergic raphe-nigral pathway. Lesions of the medial forebrain bundle causing 97% depletion of striatal DA, 72% depletion of nigral tyrosine hydroxylase, and no change in nigral glutamate decarboxylase (GAD), resulted in no change in basal or DA-stimulated cyclic AMP production ipsilateral to the injection. Lesions of the globus pallidus, causing 70% and 79% reductions in GAD and substance P respectively in the ipsilateral nigra, produced a reduction in basal cyclic AMP production and abolished the normal increase in cyclic AMP produced by DA on the side of the lesion. Lesions to the dorsal and median raphe nuclei did not affect the normal DA-sensitive adenylate cyclase response in the nigra. The results suggest that one of the neurotransmitter functions of DA in this brain region may be to modulate the release of psi-aminobutyric acid (GABA) or substance P from synaptic terminals afferent to the nigra.
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PMID:Evidence concerning the anatomical location of the dopamine stimulated adenylate cyclase in the substantia nigra. 2 89

[3H]Spiperone binding sites and the dopamine-sensitive adenylate cyclase were measured in rat substantia nigra (s. nigra) 7 or 14 days after various lesions. Hemisections, which resulted in a 66% decline in tyrosine hydroxylase and cyclic nucleotide phosphodiesterase and a 73% decrease in glutamate decarboxylase, led to a 50% decrease in [3H]spiperone binding and to the almost complete disappearance of the dopamine-sensitive adenylate cyclase from the s. nigra on the lesioned side. 6-Hydroxydopamine injection into the s. nigra, which depleted tyrosine hydroxylase activity within the s. nigra by 85%, while leaving phosphodiesterase unaffected, resulted in a 40% decrease in [3H]spiperone binding but no change in the dopamine-sensitive adenylate cyclase. Intrastriatal injections of kainic acid did not alter tyrosine hydroxylase activity in the s. nigra, but decreased both glutamate decarboxylase (54%) and phosphodiesterase (68%); [3H]spiperone binding was unaffected by this lesion while the dopamine-sensitive adenylate cyclase was greatly reduced (50-75%). These results suggest that within the s. nigra the dopamine receptor binding sites as defined using [3H]spiperone are located on dopamine neurones while the dopamine-sensitive adenylate cyclase is located presynaptically on striatonigral nerve terminals.
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PMID:Dissociation between the presynaptic dopamine-sensitive adenylate cyclase and [3H]spiperone binding sites in rat substantia nigra. 3 4

Bilateral occlusion of common carotid arteries in Mongolian gerbils was produced for the periods (up to 15 min) which were shown to be totally reversible. There was an initial increase of cyclic AMP and GABA levels and enhanced activities of adenylate cyclase and glutamate decarboxylase, as well as the reduction of norepinephrine level and decreased activities of monoamine oxidase, GABA-transaminase and Na+-K+-ATPase. Following these changes, decreased concentration of dopamine, serotinin and glutamate were found. The activities of total protein kinase and acetylcholinesterase were found to be reduced after longer periods of short-term ischemia. The data are consistent with the concept of increased non-controled release of putative neurotransmitters in ischemia.
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PMID:Alterations of putative neurotransmitters and enzymes during ischemia in gerbil cerebral cortex. 3 75

Postmortem frontal, temporal, and occipital regions of the brain from adult patients who had a diagnosis of Tourette's syndrome were analyzed for neurochemical alterations. In 3 of 4 TS-affected brains, the concentration of adenosine 3',5'-monophosphate (cyclic AMP) was reduced in all brain regions evaluated. This diminution in cyclic AMP was not associated with a significant change in the activity of the synthesizing enzyme, adenylate cyclase. No significant differences were identified for the neurotransmitter-synthesizing enzymes choline acetyltransferase and glutamate decarboxylase. Concentrations of dopamine, norepinephrine, and the serotonin metabolite 5-hydroxyindoleacetic acid were not altered. Postsynaptic receptor-binding activity for muscarinic cholinergic ([3H]quinuclidinyl benzilate) and beta receptors ([125I]iodocyanopindolol) showed no generalized impairment. It is suggested that symptoms of Tourette's syndrome might be related to an abnormality within a second messenger system.
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PMID:Tourette's syndrome: a neurochemical analysis of postmortem cortical brain tissue. 197 20

The effects of the neurotoxin aluminum on markers of synaptic neurotransmission, adenosine 3',5'-monophosphate, and neurofilaments have been evaluated in a neuroblastoma x glioma hybridoma (NG108-15). Cells were exposed for 4 days to 2 mM aluminum lactate, a concentration that did not suppress growth. Compared to controls, the activity of choline acetyltransferase was significantly increased by 37% associated with an up-regulation in enzyme activity (Vmax). Muscarinic receptors, measured by [3H]QNB binding, were reduced by 41%. In contrast, the activities of acetylcholinesterase and glutamate decarboxylase were not significantly changed. Aluminum raised the level of cyclic AMP by 20%, although adenylate cyclase activity was unchanged. Small amounts of both phosphorylated and non-phosphorylated neurofilaments were detected in NG108-15 cells. Aluminum intoxication, however, did not alter the quantity, ultrastructure, or immunoreactivity of neurofilaments. Our results demonstrate the capability of aluminum to produce selected changes in cholinergic markers and levels of cyclic AMP in a rapidly dividing cell line.
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PMID:The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma x glioma hybridoma (NG108-15). 217 66

The expression of gadA and gadB, which encode two glutamate decarboxylases (GADs) of Escherichia coli, is induced by an acidic environment and participate in acid resistance. In this study, we constructed a polyamine-deficient mutant and investigated the role of polyamines in acid resistance. The expression of gadA and gadB was shown to be dependent on polyamines. For that reason, the polyamine-deficient mutant was completely devoid of GAD activity and was very susceptible to low pH if large amounts of polyamines were not provided. We also showed that the polyamine-deficient mutant contained higher cAMP levels than the isogenic polyamine-proficient wild type, and cAMP negatively regulated the expression of gadA and gadB. Therefore, introduction of the cya (encoding adenylate cyclase) mutation allele into the polyamine-deficient mutant resulted in the increment of GAD activity and thus restored the reduced acid resistance of the mutant. The positive regulators, H-NS (histone-like protein, encoded by the hns gene) and RpoS (alternative RNA polymerase sigma subunit, encoded by rpoS gene), also significantly governed the expression of gadA and gadB, respectively. However, polyamines did not regulate either the intracellular H-NS level or rpoS expression under these culture conditions. These results strongly suggest that there are at least two different regulatory systems in acid resistance, one is positive regulation via a H-NS/RpoS system and the other is negative regulation via a polyamine/cAMP system.
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PMID:Polyamines and glutamate decarboxylase-based acid resistance in Escherichia coli. 1267 Sep 30

Pancreatic beta-cells are the major extraneural site of glutamate decarboxylase expression (GAD). During culture of isolated beta-cells, the GAD product gamma-aminobutyrate (GABA) is rapidly released in the medium, independently of insulin. It is considered as a possible mediator of beta-cell influences on alpha-cells, acinar cells, and/or infiltrating lymphocytes. In this perspective, we investigated the regulation of GABA release by rat beta-cells during a 24-h culture period. Glucose was previously reported to inhibit GABA release by diverting cellular GABA to mitochondrial breakdown through activation of GABA transferase (GABA-T). In the present study, glucagon-like peptide-1 (GLP-1) was shown to stimulate GABA formation at the level of GAD, its effect being suppressed by the GAD inhibitor allylglycine and remaining unaltered by the GABA-T inhibitor gamma-vinyl-GABA. The stimulatory action of GLP-1 is cAMP dependent, being reproduced by the adenylate cyclase activator forskolin and the cAMP analog N(6)-benzoyladenosine-3',5'-cAMP and inhibited by a PKA inhibitor. It is dependent on protein synthesis and associated with an increased expression of GAD67 but not GAD65. The GLP-1-induced stimulation of GAD activity in beta-cells can elevate medium GABA levels in conditions of glucose-driven intracellular GABA breakdown and thus maintain GABA-mediated beta-cell influences on neighboring cells.
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PMID:Glucagon-like peptide-1 stimulates GABA formation by pancreatic beta-cells at the level of glutamate decarboxylase. 1719 Sep 4

To understand the functions of the neocortex, it is essential to characterize the properties of neurons constituting cortical circuits. Here, we focused on a distinct group of GABAergic neurons that are defined by a specific colocalization of intense labeling for both neuronal nitric oxide synthase (nNOS) and substance P (SP) receptor [neurokinin 1 (NK1) receptors]. We investigated the mechanisms of the SP actions on these neurons in visual cortical slices obtained from young glutamate decarboxylase 67-green fluorescent protein knock-in mice. Bath application of SP induced a nonselective cation current leading to depolarization that was inhibited by the NK1 antagonists in nNOS-immunopositive neurons. Ruthenium red and La(3+), transient receptor potential (TRP) channel blockers, suppressed the SP-induced current. The SP-induced current was mediated by G proteins and suppressed by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), but not by inhibitors of phosphatidylinositol-specific PLC, adenylate cyclase or Src tyrosine kinases. Ca(2+) imaging experiments under voltage clamp showed that SP induced a rise in intracellular Ca(2+) that was abolished by removal of extracellular Ca(2+) but not by depletion of intracellular Ca(2+) stores. These results suggest that SP regulates nNOS neurons by activating TRP-like Ca(2+)-permeable nonselective cation channels through a PC-PLC-dependent signaling pathway.
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PMID:Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex. 2531 39