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)

The mechanism of cholinergic stimulation of alanine and glutamine formation and release from skeletal muscle was studied using rat epitrochlaris preparations. The increased alanine and glutamine release produced by carbamylcholine (10(-6) M) was reproduced by tetramethylammonium (10(-6) M) but not by pilocarpine (10(-6) M) and was blocked by hexamethonium (10(-4) M) but not by atropine (10(-7) M). This increased alanine and glutamine release was not associated with altered muscle cAMP levels. However, carbamylcholine (10(-6) M) and tetramethylammonium (10(-6) M) did not increase levels of cGMP, 134% and 101%, respectively, and these increments in cGMP were blocked by hexamethonium but not by atropine. Carbamylcholine produced a concentration-dependent increase in cGMP levels. Methylisobutylxanthine and theophylline augmented the increased amino acid release and increased cGMP levels produced by carbamylcholine. Neither xanthine derivative alone altered alanine and glutamine release or cyclic nucleotide levels. Added cGMP increased amino acid release and the uptake of [U-14C]alanine and alpha-amino[14C]isobutyric acid. Carbamylcholine did not alter muscle phosphorylase a activity, glycogen levels, or basal adenylate cyclase activity. These data indicate that cholinergic stimulation of muscle alanine and glutamine formation and release involves a nicotinic cholinergic receptor and may be mediated by increased levels of cGMP, which in turn may result from a cholinergic stimulation of muscle guanylyl cyclase.
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PMID:Cholinergic stimulation of skeletal muscle alanine and glutamine formation and release. Evidence for mediation by a nicotinic cholinergic receptor and guanosine 3':5'-monophosphate. 8 Dec 8

Isolated kidney cortex tubules from starved rats have been used to study the actions of catecholamines on renal adenosine 3':5' monophosphate (Ado-3':5'-P) levels and gluconeogenesis. In accordance with previous workers, norepinephrine was found to increase glucose formation from lactate and pyruvate and to a smaller degree from malate, succinate, fumarate and glutamine. The stimulatory effect of 0.5 muM norepinephrine was additive to that of 0.1 mM Ado-3':5-P, indicating an Ado-3':5'-P-independent mechanism of catecholamine action. The effects of parathyroid hormone and oleate on gluconeogenesis were also additive to that of norepinephrine. A comparative study of the actions of different catecholamine derivatives revealed that gluconeogenesis was stimulated in parallel to the alpha-adrenergic potency of the hormones, whereas Ado-3':5'-P levels were increased according to the known beta-stimulatory potency of the agents. Although isoproterenol was by far the most effective in raising Ado-3':5'-P levels, it was without effect on glucose formation from pyruvate, when added at 0.1 muM. At the same concentration, phenylephrine, which had no effect on Ado-3':5'-P levels, was the best stimulator of gluconeogenesis. The alpha-receptor blocking agent phentolamine inhibited the stimulatory effect of catecholamines on gluconeogenesis with a 50 times higher potency than propranolol, a beta-blocking agent. The fact that the stimulatory effect of Ado-3':5'-P was also blocked by propranolol, indicated an unspecific mechanism of action of this substance. The results indicate that the stimulatory effect of catecholamines on renal gluconeogenesis are mediated by an alpha-receptor and that they are independent from the stimulation of renal adenyl cyclase by these agents.
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PMID:Metabolism of isolated kidney tubules. Independent actions of catecholamines on renal cyclic adenosine 3':5'-monophosphate levels and gluconeogenesis. 17 87

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62

The mechanism of the increased alanine and glutamine formation and release from skeletal muscle in experimental uremia was investigated using epitrochlearis preparations from control and chronically uremic rats. In uremic muscle, insensitivity to epinephrine or serotonin suppression of alanine and glutamine release was observed. With control muscles, 1 nm or greater, epinephrine inhibited alanine and glutamine release, whereas with uremic muscles, epinephrine concentrations <1 muM did not alter amino acid release. Decreased alanine and glutamine release with 1 nM serotonin was observed in control muscles, but no inhibition was observed with concentrations <1 muM in uremic muscle. Muscle amino acid levels were the same in control and uremic muscles in the presence or absence of epinephrine or serotonin. The reutilization of released alanine by protein synthesis or oxidation to CO(2) was not differentially affected by epinephrine in uremic muscles as compared with control muscle. Dibutyryl-cAMP inhibited amino acid release equally in uremic and control muscles. Epinephrine or serotonin increased cAMP levels two- to four-fold or more in control than in uremic muscle. Basal- and fluoride-stimulated adenylate cyclase activities were equal in uremic and control muscle homogenates and in membrane fractions, but 10 muM epinephrine-stimulated adenylate cyclase was reduced 30-60% with uremia. At any concentration of epinephrine (0.001-100 muM), the stimulation of membrane adenylate cyclase activity was one- to twofold greater with control membranes than with uremic muscle membranes. With either control or uremic muscle, peak adenylate cyclase activity was observed at 1 muM epinephrine. These data indicate that skeletal muscle in chronic uremia acquires an insensitivity to the metabolic action of epinephrine or serotonin. This insensitivity may be attributable in part to the diminished increments in muscle cAMP levels produced by adrenergic and serotonergic agonists. The decreased cAMP levels may derive in turn from a decreased activity or subsensitization of the agonist-stimulated adenylate cyclase in uremic muscle.
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PMID:The regulation of skeletal muscle alanine and glutamine formation and release in experimental chronic uremia in the rat: subsensitivity of adenylate cyclase and amino acid release to epinephrine and serotonin. 21 Nov 45

Neuroblastoma cells were synchronized by a combined isoleucine plus glutamine starvation. Adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was measured under basal conditions and in the presence of dopamine, adenosine and prostaglandin (PG) E1. A clear dissociation occurred between the respective evolution patterns of basal and agonist-stimulated adenylate cyclase activities. The magnitudes of the enzyme response to PGE1, adenosine, and dopamine also exhibited different evolution patterns during the cell cycle. Evolution of adenylate cyclase responsiveness to PGE1 during the cell cycle exhibited striking similarities with the intracellular 3':5'-cyclic AMP changes observed elsewhere. Use of theophylline and fluphenazine as specific inhibitors of adenosine and dopamine, respectively, made it possible to demonstrate that adenosine, dopamine, and PGE1 stimulated adenylate cyclase through independent receptor sites. Furthermore, whatever the stage of the cell cycle, responses to these three agonists were not additive, indicating that the receptors of adenosine, dopamine, and PGE1 control the same adenylate cyclase moieties. The data suggest that adenylate cyclase cell content and enzyme responsiveness to specific agonists can be independently controlled.
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PMID:Adenylate cyclase from synchronized neuroblastoma cells: responsiveness to prostaglandin E1, adenosine, and dopamine during the cell cycle. 26 97

Mouse neuroblastoma cells derived from cholinergic clone NS 20 were synchronized by isoleucine plus glutamine starvation. Basal adenylate cyclase activity increased linearly during the different phases of the cell cycle. Pharmacological data are presented indicating that adenosine, dopamine and prostaglandin E1 control through distinct receptors the same adenylate cyclase activity. The demonstration that basal enzyme activity and its responsiveness to the three agonists tested followed different evolution patterns during the cell cycle suggests that enzyme activity (or content) and activity (or number) of enzyme coupled receptors can be independently modulated.
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PMID:[Adenylate cyclase in synchronized neuroblastoma cells: enzyme response during the cell cycle]. 82 49

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.
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PMID:Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside. 132 94

Mammalian spermatogenesis consists of a series of complex developmental processes controlled by the pituitary-hypothalamic axis. This flow of biochemical information is directly regulated by the adenylate cyclase signal transduction pathway. We have previously described the CREM (cyclic AMP-responsive element modulator) gene which generates, by cell-specific splicing, alternative antagonists of the cAMP transcriptional response. Here we report the expression of a novel CREM isoform (CREM tau) in adult testis. CREM tau differs from the previously characterized CREM antagonists by the coordinate insertion of two glutamine-rich domains that confer transcriptional activation function. During spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ cells CREM is expressed at low amounts in the antagonist form. Subsequently, from the pachytene spermatocyte stage onwards, a splicing event generates exclusively the CREM tau activator, which accumulates in extremely high amounts. This splicing-dependent reversal in CREM function represents an important example of developmental modulation in gene expression.
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PMID:Developmental switch of CREM function during spermatogenesis: from antagonist to activator. 137 May 76

The objective of this study was to determine whether L-glutamate (L-Glu) may serve as a neurotransmitter candidate in the guinea pig myenteric plexus. We observed that [3H]Glu and gamma-[3H]aminobutyric acid were synthesized from [3H]glutamine and released from neurons of the myenteric plexus during K+ and 1,1-dimethyl-4-phenylpiperazinium-evoked depolarization in a concentration-dependent manner. Muscle tension studies performed on ileal longitudinal muscle-myenteric plexus (LM-MP) preparations revealed that L-Glu [mean effective dose (ED50) 2.5 x 10(-5) M] produced concentration-dependent contractions, which were unaffected by hexamethonium but abolished by tetrodotoxin, atropine, and magnesium, suggesting that L-Glu acts via N-methyl-D-aspartate (NMDA)-type receptors that stimulate a cholinergic neural pathway unaffected by ganglionic blockade. In addition, L-Glu (ED50 4 x 10(-5) M) and NMDA (ED50 2 x 10(-4) M) stimulated concentration-dependent release of [3H]acetylcholine (ACh) from LM-MP sections, which was inhibited by tetrodotoxin, magnesium, and the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (AP-5). L-Glu-mediated release of [3H]ACh was enhanced by theophylline (10-6 M) and 3-isobutyl-1-methylxanthine (1 mM) and was significantly reduced by the adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (10(-4) M) and somatostatin-14 (10(-6) M), which inhibits adenosine 3',5'-cyclic monophosphate (cAMP)-dependent cholinergic transmission in the myenteric plexus. These studies suggest that L-Glu may serve as an excitatory neurotransmitter in the myenteric plexus via its action on NMDA-type receptors, which are coupled to cAMP-dependent release of ACh.
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PMID:Evidence for a glutamatergic neural pathway in the myenteric plexus. 168 38

Using PCR technology, we have cloned parts of three developmentally regulated putative serine/threonine kinases from Dictyostelium. All show significant homology to members of the cAMP-dependent protein kinase A/protein kinase C subfamilies. A genomic clone encoding one of these, DdPK3, has been isolated and sequenced. The open reading frame encodes a protein of 648 amino acids with the conserved kinase domain in the C-terminal half. The protein encoded by this gene is unusual in that it contains long homopolymer runs in the N-terminal half of the protein, including a long run of 88 amino acids in which 73 are glutamine residues. To examine the function of DdPK3, a gene disruption was created via homologous recombination. Ddpk3- cells do not aggregate by themselves but will co-aggregate with wild-type cells. However, after aggregation these cells are 'sloughed off' and do not proceed further through development, but are found as a discrete mass alongside the fruiting body formed by the wild-type cells. Analysis of signal transduction pathways indicates that cAMP pulse-induced expression of aggregation stage-specific genes is normal in Ddpk3- cells, as is induction of the prestalk gene Ddras in single cell assays. However, cAMP induction of the late promoters of cAMP receptor cAR1 and of two prespore-specific genes is absent under similar conditions. These cells show normal activation of adenylate cyclase and normal phosphorylation of the G alpha protein G alpha 2 in response to cAMP. The possible role of DdPK3 in Dictyostelium development is discussed.
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PMID:A developmentally regulated, putative serine/threonine protein kinase is essential for development in Dictyostelium. 183 54


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