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)

A chemical relatedness has been described between the beta-subunit of cholera toxin and that of the four dimeric glycoprotein hormones (hCG, hLH, hFSH and hTSH). However, antibodies induced by cholera toxin did not crossreact, when tested by labeled hCG binding and immunocytochemistry, with the beta-subunit of hCG. It appears that differences in the tertiary structures, as shown in this study, account for distinct epitopes. Similarities in biological activity between these two compounds, such as induction of adenyl cyclase or a protective effect against some tumors, are not based on immunological mechanisms.
...
PMID:Lack of immunological analogy between the beta-subunits of cholera toxin and human choriogonadotropin. 242 25

The role of cyclic adenosine 3':5'-monophosphate (cAMP) in the regulation of the synthesis and release of glycoproteins and of carcinoembryonic antigen by colon cancer cells was studied using LS174T cells in vitro. Adenylate cyclase and cAMP phosphodiesterase activities were assessed by measuring cellular cAMP in response to forskolin and cholera toxin (adenylate cyclase activators) and to 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). Each agent increased cAMP levels significantly. Dibutyryl-cAMP (1 mM) stimulated glycoprotein synthesis and release when [3H]fucose was used as a precursor. The synthesis and release of carcinoembryonic antigen, a membrane-associated glycoprotein antigen, was also significantly increased by these test agents. A close dose-response relationship existed for forskolin and for cholera toxin between cAMP generation and carcinoembryonic antigen release. cAMP may play a role in regulating the synthesis and release of glycoprotein antigens by colon cancer cells.
...
PMID:Effects of cyclic adenosine 3':5'-monophosphate upon glycoprotein and carcinoembryonic antigen synthesis and release by human colon cancer cells. 242 31

Antibodies directed against the major apoprotein of rabbit lung surfactant, a 29-36-kDa glycoprotein, were used to study changes in the levels of translatable surfactant apoprotein mRNA in rabbit lung tissue during development, as well as the effects of cortisol and cyclic AMP analogues on the levels of surfactant apoprotein and its mRNA in fetal rabbit lung tissue in organ culture. The major surfactant apoprotein and its mRNA were undetectable in lung tissues of 21-day gestational age fetal rabbits. Translatable mRNA specific for the major surfactant apoprotein was first detectable in lung tissues of 26-day fetuses, increased 25-fold on day 28, reached peak levels at day 31, and declined after birth. Incubation of 21-day fetal rabbit lung explants with cortisol in serum-free medium resulted in an increase in the specific content of the 29-36-kDa apoprotein. Cyclic AMP analogues and forskolin, an activator of adenylate cyclase, also caused a marked increase in the accumulation of surfactant apoprotein. When fetal lung explants were incubated with cortisol and dibutyryl cyclic AMP in combination, the specific content of the surfactant apoprotein was increased to levels greater than that of explants treated with either cortisol or dibutyryl cyclic AMP alone. These effects of dibutyryl cyclic AMP and cortisol on surfactant apoprotein accumulation were associated with comparable changes in the levels of translatable surfactant apoprotein mRNA. Thus, we have shown for the first time that the induction of pulmonary surfactant apoprotein synthesis during differentiation in vitro and in vivo is associated with an increase in the level of translatable mRNA and that cortisol and cyclic AMP increase both the accumulation of the major surfactant apoprotein and the corresponding mRNA in fetal rabbit lung tissue in vitro.
...
PMID:Regulation of the synthesis of the major surfactant apoprotein in fetal rabbit lung tissue. 242 57

The use of beta-adrenergic agonists in the treatment of preterm labor has been found to be associated with a decreased incidence of respiratory distress syndrome (RDS) in premature newborns. beta-Sympathomimetic agents, which activate adenylate cyclase and increase tissue cAMP levels, as well as cAMP analogs stimulate surfactant glycerophospholipid synthesis and secretion by fetal lung tissue. In the present study, we used antibodies directed against the major human pulmonary surfactant apoprotein, a 35,000-dalton glycoprotein, to evaluate the effects of the cAMP analog dibutyryl cAMP (Bt2cAMP) and the beta-adrenergic agonist terbutaline on surfactant apoprotein synthesis in human fetal lung explants in organ culture. By use of immunoblot analysis, we found that Bt2cAMP (1 mM) markedly stimulated accumulation of the major surfactant apoprotein in human fetal lung explants, as did terbutaline. Bt2cAMP treatment also increased the relative rate of incorporation of [35S]methionine into the major surfactant apoprotein. The Bt2cAMP-induced increase in surfactant apoprotein synthesis and accumulation was associated with an increase in the levels of translatable surfactant apoprotein mRNA. Morphometric analysis at both the light and electron microscopic levels was used to evaluate the effects of Bt2cAMP on the morphology of the human fetal lung in vitro. After 48-h incubation with Bt2cAMP, the prealveolar ducts of the fetal lung explants were enlarged greatly, and the relative amount of interalveolar connective tissue was reduced compared to those in control tissues. The volume density of type II cells in the Bt2cAMP-treated explants was significantly greater than that in control explants at this time point; however, after 4 and 6 days of incubation, the volume density of type II cells in control and Bt2cAMP-treated tissues was similar, and the lumina of the prealveolar ducts of control tissues had a volume density similar to that of Bt2cAMP-treated explants. Bt2cAMP also had pronounced effects on the ultrastructural morphology of the human fetal lung explants. Large quantities of secreted lamellar bodies and tubular myelin were observed in the lumina of the prealveolar ducts of the Bt2cAMP-treated tissue. Few lamellar bodies and no tubular myelin were observed in the lumina of the prealveolar ducts of control tissues. These findings suggest that cAMP may serve an important regulatory role in the synthesis and secretion of the major surfactant apoprotein by human fetal lung.
...
PMID:Adenosine 3',5'-monophosphate analogs and beta-adrenergic agonists induce the synthesis of the major surfactant apoprotein in human fetal lung in vitro. 244 78

The Ca2+ antagonist binding sites associated with the voltage dependent calcium channel in rabbit myocardium were found to distribute with the sarcolemmal Na+ + K+ ATPase and adenylate cyclase activities during subcellular fractionation on sucrose-density gradients. The equilibrium dissociation constants (KD) for the binding of [3H]nitrendipine and [3H]verapamil were 0.31 +/- 0.04 nM and 4.1 +/- 0.5 nM respectively, and displayed an average density of 0.55 +/- 0.05 pmol/mg and 0.4 +/- 0.03 pmol/mg protein respectively for the most enriched membrane fraction. The Ca2+ antagonist binding sites were solubilized from the membranes with the detergent 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate, and specific binding sites for [3H]PN200-110, [3H]verapamil and [3H]diltiazem were isolated on a wheat-germ lectin column. The binding sites for [3H]PN200-110 were enriched about 2,500 fold as compared with the original homogenate and displayed a density of 28.5 +/- 8 pmole/mg protein in the isolated fraction. Sodium dodecyl sulfate gel electrophoresis of the isolated drug binding proteins indicated enrichment of proteins of Mr 170,000, 140,000, 130,000, 100,000 and 53,000. The isolated receptor contained an intrinsic kinase activity that phosphorylated glycoproteins of Mr 170,000 and 53,000. Exogenously added cAMP-kinase stimulated phosphorylation of the 170,000, 100,000, 53,000 and 28,000 Mr glycoproteins in the receptor fraction. The results of this study indicate that the binding sites for [3H]nitrendipine, [3H]PN200-110, [3H]verapamil and [3H]diltiazem residue on glycoprotein(s) which are of sarcolemmal origin, and co-purify together on wheat germ lectin columns. The polypeptide composition of the Ca2+ antagonist binding sites from cardiac muscle appears to be very similar to that of the dihydropyridine receptor in skeletal muscle.
...
PMID:Subcellular distribution and isolation of the Ca2+ antagonist receptor associated with the voltage regulated Ca2+ channel from rabbit heart muscle. 244 72

Synthetic peptides, representing specific portions of the alpha-subunit of the human glycoprotein hormones, can inhibit both the binding of labeled TSH to thyroid membranes and adenylate cyclase stimulation by TSH in vitro. The same synthetic peptides (alpha 26-46 and alpha 31-45) significantly (P less than 0.05) inhibited the adenylate cyclase-stimulating activity of thyroid-stimulating immunoglobulins (TSI) from 10 patients with hyperthyroid Graves' disease. Peptide alpha 26-46 was the most potent, resulting in 79.1 +/- 8.8% (+/- SE) inhibition at 133 micrograms/mL, while peptide alpha 31-45 inhibited TSI activity by 36.3 +/- 5.2%. Peptides alpha 61-75 and alpha 81-92, that had only minimal ability to inhibit TSH-mediated cAMP generation, did not significantly inhibit TSI activity. The inhibitory action of alpha 26-46 was dose dependent, and a significant negative correlation was found between the maximum TSI activity of the serum sample and the inhibition achieved by the synthetic peptide, suggesting that differences in TSI affinity and/or titer may account for the variable inhibitory activity of the peptides. These results suggest that TSI interact with the TSH receptor at the site that recognizes the portion of the TSH alpha-subunit represented by the synthetic peptide alpha 26-46 and, thus, support the concept that the TSH-binding site of the TSH receptor is the site of antigen binding between TSI and the thyroid cell.
...
PMID:The effects of synthetic alpha-subunit peptides on thyroid-stimulating immunoglobulin activity. 245 77

The follicle-stimulating hormone (FSH) receptor purified from calf bovine testis membranes appears to be an oligomeric glycoprotein, consisting of 4 disulfide-linked monomers of molecular weight about 60,000 each. Polyclonal antibodies to the hormone binding sites of the receptor have been developed. FSH interaction with the receptor seems to involve multiple discrete binding regions, which include amino acids 34-37 and 49-52 of the human FSH beta subunit. The interaction between FSH and the membrane-bound receptor is reversible at low temperatures but becomes increasingly irreversible as the temperature increases. FSH interaction with the soluble receptor is reversible over a wider temperature range. The hydrophobic effect is a significant factor in the initial hormone receptor interaction in each system. FSH bound to membrane receptors on cultured immature rat Sertoli cells is internalized and degraded to the level of amino acids. Current evidence suggests that the membrane receptor may exist as free receptor, and complexed with G-protein. A functional receptor/G-protein/adenylate cyclase complex has been reconstituted in liposomes. The G-protein of testis membranes contains both high and low affinity guanosine triphosphate (GTP) binding sites. Both are capable of modulating FSH receptor binding, whereas only the high affinity sites seem to be required for activation of adenylate cyclase. Although testis membranes contain a phosphatidylinositide hydrolysis system, the latter is not directly influenced by FSH.
...
PMID:The follicle-stimulating hormone (FSH) receptor in testis: interaction with FSH, mechanism of signal transduction, and properties of the purified receptor. 249 20

An octopamine receptor photoaffinity probe was used to label membranes from the light organs of Photinus pyralis, a tissue highly enriched in octopamine receptors. Labeling was concentrated in a glycoprotein of 75 +/- 2 kDa with lesser labeling of a 79 +/- 2 kDa component. Labeling could be displaced by prior incubation with octopamine, mianserin, cyproheptadine, phentolamine or propranolol, with a relative potency that correlated with the ability of these same agents to modulate light organ octopamine-sensitive adenylate cyclase. The 75 kDa binding protein was isolated and its N-terminal amino acid sequence was determined.
...
PMID:Isolation and N-terminal amino acid sequence of an octopamine ligand binding protein. 251 33

The plasticizers tris-(2-butoxyethyl)-phosphate (TBEP) and di-(2-ethylhexyl)-phthalate (DEHP) and the beta-adrenergic receptor-blockers [3H]-(-)-dihydroalprenolol ([3H]-(-)-DHA) and [3H]-(-)-CGP 12177 were tested for their ability to interact with beta-adrenergic binding to alpha 1-acid glycoprotein (AAG) and mononuclear leukocytes (MNL). The IC50-values, obtained by displacement of [3H]-(-)-DHA bound to AAG, were 3.5 nM, 2 microM and 4 microM for TBEP, (-)-alprenolol and DEHP, respectively. (+/-)-CGP 12177 had virtually no effect on radioligand binding to AAG. The [3H]-(-)-CGP 12177 binding to MNL consisted of beta-adrenergic receptor binding (Kd = 210 pM) and non-saturable binding. [3H]-(-)-DHA was bound to two different classes of binding sites on MNL, the beta-adrenergic receptors (Kd = 440 pM) and a secondary class of binding sites (Kd = 64 nM). (+/-)-CGP 12177 displaced about 30% of [3H]-(-)-DHA from MNL with an IC50-value of 190 pm. (-)-ALP displaced about 85% of total bound radioligand and gave a biphasic displacement curve with IC50-values of 320 pM and 690 mM, respectively. TBEP displaced a considerable fraction of [3H]-(-)-CGP 12177 and [3H]-(-)-DHA bound to MNL beta-adrenergic receptors, whereas DEHP had no effect. In contrast, DEHP caused displacement of [3H]-(-)-DHA from the MNL low affinity sites, but was a markedly less potent displacer compared to TBEP. The present study shows that TBEP and DEHP interact with beta-adrenergic transport proteins, non-specific tissue binding sites and beta-adrenergic receptors coupled to adenylate cyclase. Plasticizers may thus affect the biology and pharmacology of the beta-adrenergic signal system.
...
PMID:The effect of the plasticizers TBEP (tris-(2-butoxyethyl)-phosphate) and DEHP (di-(2-ethylhexyl)-phthalate) on beta-adrenergic ligand binding to alpha 1-acid glycoprotein and mononuclear leukocytes. 254 84

Inhibitors of N-linked oligosaccharide processing are useful tools for studies on the biological function of the oligosaccharide structures in glycoprotein hormones. We have synthesized molecules of lutropin (LH) containing high-mannose- and hybrid-type oligosaccharides using rat gonadotroph-enriched primary cultures in the presence of castanospermine (a glucosidase I inhibitor) or swainsonine (a mannosidase II inhibitor), in order to compare the actions of these molecules with that of the hormone containing complex-type oligosaccharides in the activation of the receptor-adenylate cyclase system. Treatment of gonadotrophs with the above inhibitors caused an increase in the synthesis of highly basic LH molecules (pI 9.6-10.0), because addition of charged carbohydrate moieties to these molecules was prevented. Characterization of the oligosaccharide structure performed by enzymatic treatment (endoglycosidase H and neuraminidase) and the use of immobilized lectins (wheat germ agglutinin and Ricinus communis agglutinin-120) showed that these inhibitor-synthesized LH molecules contained high-mannose- and hybrid-type (asialo and sialylated) oligosaccharides. Their immunological properties were similar to that of complex-type oligosaccharide LH, but they had significantly higher receptor-binding ability in comparison with a sialylated complex-type oligosaccharide LH (about 12-fold) and an asialo complex-type oligosaccharide LH (about 3-fold). It was noted that the incompletely processed molecules were less potent than complex-type oligosaccharide LH in the activation of adenylate cyclase of Leydig cells, showing about 40-60% of the activity induced by the sialylated complex-type oligosaccharide molecule. The present data indicate that the inhibition of terminal processing of N-linked oligosaccharides by castanospermine and swainsonine impairs the full hormonal function of rat LH.
...
PMID:Incompletely processed LH molecules synthesized by rat gonadotrophs treated with inhibitors of oligosaccharide processing. 255 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---