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)

Ethanol was shown to activate adenylate cyclase in mouse striatal membranes, but significant activation of adenylate cyclase by ethanol concentrations below 500 mM was found only in the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p] or other guanine nucleotides. Ethanol did not alter the amount of guanine nucleotide required for half-maximal activation of adenylate cyclase, but was found to further increase adenylate cyclase activity under conditions wherein the nucleotide binding protein was preloaded with Gpp(NH)p or when hydrolysis of added GTP was blocked using cholera toxin. The stimulation of adenylate cyclase activity by sodium fluoride was also accentuated by ethanol. Ethanol, propanol and butanol all increased adenylate cyclase activity in the presence of Gpp(NH)p, and their effects on adenylate cyclase activity were linearly correlated with their respective carbon chain lengths. Equivalent membrane concentrations of ethanol and chloroform produced similar increases in adenylate cyclase activity under conditions where hydrolysis of added GTP was inhibited. However, chloroform and ethanol had opposite effects on adenylate cyclase activity in assays containing GTP and membranes not treated with cholera toxin. The apparent Km of adenylate cyclase for Mg-ATP and the Arrhenius activation energy for the enzyme in membranes incubated with Gpp(NH)p were similar in the presence and absence of ethanol. Ethanol, in concentrations up to 750 mM, did not alter the pattern of stimulation of adenylate cyclase by calcium and calmodulin. Our results suggest that ethanol modifies the equilibrium for the interaction of the nucleotide-loaded G-protein with the catalytic unit of adenylate cyclase to favor formation of the active nucleotide-G-protein-catalytic unit complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of adenylate cyclase by alcohols requires the nucleotide-binding protein. 670 9

Previously, a 5-hydroxytryptamine receptor has been described in neuronal membrane preparations. This receptor corresponds to a recognition site for 5-HT, and is seemingly related to an effector which consists of an adenylate cyclase activated by 5-HT and having a high apparent affinity constant (KD close to 1 nM). Moreover, this neuronal receptor is distinct of the glial serotoninergic receptor (Fillion et al., 1980). The method used to measure the binding of 3H-5-HT has been previously reported (FILLION et al., 1978). Adenylate cyclase activity was determined by measurement of cAMP using a radioimmunoassay (FILLION et al., 1979 a, b). Membranes were pretreated as follows: (1) membranes were preexposed to 5-HT (i.e.: incubated in the presence of 5-HT, generally 10 nM) at 37 degrees C, washed by centrifugation and resuspended in a medium free of 5-HT (or diluted in the same medium) or (2) membranes were incubated with a single concentration of 5-HT for a prolonged duration. Results were as follows: 1. The binding of 3H-5-HT, incubated for 10 min at 37 degrees C, corresponds to a KD close to 20 nM whereas a prolongation of the incubation duration to 15-25 induces the binding of 5-HT with a KD close to 2 nM. 2. Preexposure of the membranes to 5-HT leads to the same increase in affinity with, apparently, a reduced number of sites. 3. N-ethylmaleimide pretreatment of the membranes prior to their preexposure to 5-HT inhibits the change in affinity. 4. GTP, but not GDP, reverses the affinity change. 5. The adenylate cyclase activated by 5-HT is desensitized by preexposure of the membranes to 5-HT. 6. GTP reverses the process of desensitization. These results support the hypothesis of the existence of a regulatory mechanism for the 5-HT neuronal receptor. The regulatory mechanism would involve structural conformation changes of the recognition site corresponding to different affinities of the adenylate cyclase. A nucleotide binding protein is presumably involved in the coupling of these two subunits of the receptor.
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PMID:[Increase in binding affinity of the 5-HT receptor and decrease in 5-HT sensitive adenylate cyclase activity following prolonged exposure to 5-HT (author's transl)]. 728 51

The existence of a cAMP-dependent regulation of the expression of the alpha-subunit of the stimulatory guanine nucleotide-binding protein (Gs) in a well characterized astroglial cells culture was established. The culture of astroglial cells for 3-6 h with isoproterenol (10 microM) or forskolin (10 microM) (a cAMP-inducing agent) increased (200-400%) the response of adenylylcyclase to agents which bypass the receptor; GTP, GTP[S] or forskolin. For prolonged exposure times (15 h or more) to isoproterenol or forskolin, the adenylycyclase activity decreased to the value observed in control cells. The same biphasic response of adenylylcyclase to isoproterenol (10 microM) plus GTP (10 microM) occurred in membrane fractions from cells cultured with forskolin, whereas a diminished response to isoproterenol was observed in isoproterenol-treated cells, indicating that the beta-adrenergic receptor was desensitized. To understand the molecular mechanism of these phenomena, we measured the levels of the alpha subunits of the guanine-nucleotide binding protein (Gs and Gi) by Western-blot analysis. The culture of astroglial cells with isoproterenol or forskolin (3-24 h) resulted in a transient increase of both the Gs alpha and the Gi alpha protein levels, while the level of G beta subunits was unaffected. We also identified Gs alpha protein (about 40% of the total cellular protein) in the supernatant fraction of astroglial cells but its level was not modified by the stimulation of cells by forskolin. The level of Gs alpha mRNA measured by Northern-blot analysis was transiently increased (200%) after stimulation of astroglial cells with isoproterenol or forskolin for an incubation period of 6-9 h, then returned to that of control cells for longer period of time. In addition, the Gs alpha mRNA level was threefold increased when cells were cultured for 2-6 h with 8-bromoadenosine 3':5'-cyclic monophosphate (10 microM), a permeant analogue of cAMP. These results indicate that cAMP induces a time-dependent increase of Gs alpha mRNA. The half-life of Gs alpha protein and Gs alpha mRNA were determined. Pulse-chase studies revealed that the decay of Gs alpha protein was clearly biphasic with an early phase (5-6 h) and a slower second phase (20-25 h) but the treatment of cells with forskolin did not accelerate or slow down the turnover of Gs alpha protein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclic AMP regulation of messenger RNA level of the stimulatory GTP-binding protein Gs alpha. Isoproterenol, forskolin and 8-bromoadenosine 3':5'-cyclic monophosphate increase the level of Gs alpha mRNA in cultured astroglial cells. 750 89

Based on the similarity of genes which code for guanine-nucleotide binding protein- (G-protein-) coupled receptors, cDNA clones encoding new members of the receptor family have been isolated from Bombyx mori and Heliothis virescens. The deduced protein structures exhibit highest similarity to tyramine/octopamine and serotonin receptors of Drosophila. One of the receptor clones (K50Hel) was permanently expressed in the mammalian cell line LLC-PK1. In stimulation experiments its responded to octopamine leading to an inhibition of adenylate cyclase activity in a dose-dependent manner. Pharmacological studies revealed a higher affinity for mianserin than for yohimbine suggesting, that the K50Hel clone encoded a neuronal type 3 octopamine receptor. As revealed by in situ hybridization, this receptor type is expressed in the central nervous system and antennae of moth.
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PMID:Cloning of biogenic amine receptors from moths (Bombyx mori and Heliothis virescens). 901 28

In this paper the authors examine current findings on the etiology of fibrous dysplasia. Particular emphasized is the role of the biochemical pathways and the genetic mutations occurring in the disease. In fact it is demonstrated that the McCune-Albright syndrome, a variant of fibrous dysplasia, is caused by the mutations of the GNAS 1 gene that codify for the alfa-subunit of the stimulatory guanine-nucleotide binding protein (G-protein). This mutation activates adenylate cyclase and consequently increases intracellular concentrations of cAMP. The increased signaling through the cAMP is believed to be responsible for the clinical characteristic of the McCune-Albright syndrome. The cap is translocated to the nucleus where a family of transcription factors is phosphorylated. This group of factors regulates the expression of CAp responsive genes: one of them, the c-fos proto-oncogene, produces a nuclear protein that binds with other proteins encoded by c-jun proto-oncogene, to form a transcription factor, AP-1. Several studies have shown an increase of c-fos mRNA in the bone lesions of patients with fibrous dysplasia. It suggests that the overexpression of c-fos may represent the first step in the carcinogenesis of bone sarcomas. Finally, attention is focused on the intravenous use of pamidronate as medical management in the treatment of the lesions that are not susceptible to surgical treatment.
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PMID:[Fibrous dysplasia. The clinico-therapeutic picture and new data on its etiology. A review of the literature]. 957 46

Fission yeast adenylate cyclase is activated by the gpa2 Galpha subunit of a heterotrimeric guanine-nucleotide binding protein (G protein). We show that the git5 gene, also required for this activation, encodes a Gbeta subunit. In contrast to another study, we show that git5 is not a negative regulator of the gpa1 Galpha involved in the pheromone response pathway. While 43% identical to mammalian Gbeta's, the git5 protein lacks the amino-terminal coiled-coil found in other Gbeta subunits, yet the gene possesses some of the coding capacity for this structure 5' to its ORF. Although both gpa2 (Galpha) and git5 (Gbeta) are required for adenylate cyclase activation, only gpa2 is needed to maintain basal cAMP levels. Strains bearing a git5 disruption are derepressed for fbp1 transcription and sexual development even while growing in a glucose-rich environment, although fbp1 derepression is half that observed in gpa2 deletion strains. Multicopy gpa2 partially suppresses the loss of git5, while the converse is not true. These data suggest that Gbeta is required for activation of adenylate cyclase either by promoting the activation of Galpha or by independently activating adenylate cyclase subsequent to Galpha stimulation as seen in type II mammalian adenylate cyclase activation.
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PMID:The fission yeast git5 gene encodes a Gbeta subunit required for glucose-triggered adenylate cyclase activation. 1074 45

The fission yeast Schizosaccharomyces pombe responds to environmental glucose by activating adenylate cyclase. The resulting cAMP signal activates protein kinase A (PKA). PKA inhibits glucose starvation-induced processes, such as conjugation and meiosis, and the transcription of the fbp1 gene that encodes the gluconeogenic enzyme fructose-1,6-bisphosphatase. We previously identified a collection of git genes required for glucose repression of fbp1 transcription, including pka1/git6, encoding the PKA catalytic subunit, git2/cyr1, encoding adenylate cyclase, and six "upstream" genes required for adenylate cyclase activation. The git8 gene, identical to gpa2, encodes the alpha subunit of a heterotrimeric guanine-nucleotide binding protein (Galpha) while git5 encodes a Gbeta subunit. Multicopy suppression studies with gpa2(+) previously indicated that S. pombe adenylate cyclase activation may resemble that of the mammalian type II enzyme with sequential activation by Galpha followed by Gbetagamma. We show here that an activated allele of gpa2 (gpa2(R176H), carrying a mutation in the coding region for the GTPase domain) fully suppresses mutations in git3 and git5, leading to a refinement in our model. We describe the cloning of git3 and show that it encodes a putative seven-transmembrane G protein-coupled receptor. A git3 deletion confers the same phenotypes as deletions of other components of the PKA pathway, including a germination delay, constitutive fbp1 transcription, and starvation-independent conjugation. Since the git3 deletion is fully suppressed by the gpa2(R176H) allele with respect to fbp1 transcription, git3 appears to encode a G protein-coupled glucose receptor responsible for adenylate cyclase activation in S. pombe.
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PMID:Glucose monitoring in fission yeast via the Gpa2 galpha, the git5 Gbeta and the git3 putative glucose receptor. 1101 2


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