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)

Human chorionic gonadotrophin (hCG) increased cyclic adenosine monophosphate (cAMP) in pieces of eel ovary in vitro. Although the ED50 (about 0.1 micrograms/ml) was the same as for carp gonadotrophin (cGTH), the maximal stimulation (close to 3 times basal level) was about 10 times lower than that for the fish hormone. The mechanism of this atypical action of hCG was studied using different approaches. Human CG did not inhibit the action of cGTH. Desensitization experiments (cGTH or hCG being injected in vivo 18 hr before the sampling of the ovary) were carried out; the in vitro action of hCG was suppressed by both pretreatments; the in vitro action of cGTH was largely reduced by in vivo cGTH and to a much lesser extent by in vivo hCG. Together with other data the results indicated that hCG acts via binding to adenylate cyclase-coupled receptors which also recognize cGTH; moreover, they suggested that among those systems only a fraction can be activated by hCG. We propose that in teleosts the pool of GTH receptors is not homogeneous but contains classes of "isoreceptors" differing by their recognition specificity at least. Parallel studies with ovine lutrophin (oLH) indicated that this hormone binds to the same adenylate cyclase-coupled receptors which are sensitive to hCG but that it does it with a much lower affinity. Other characteristics of oLH/hCG-stimulated receptor-adenylate cyclase systems include an important release of cAMP into the incubation medium. The precise physiological significance of GTH "isoreceptors" still requires clarification. The ability of hCG to induce desensitization must be considered in fish culture experiments using this hormone.
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PMID:Human chorionic gonadotrophin and immature fish ovary: characterization and mechanism of the in vitro stimulation of cyclic adenosine monophosphate accumulation. 298 65

Cultured NCB-20 hybrid cells express adenylate cyclase-coupled receptors for 5-hydroxytryptamine (5-HT) that correspond biochemically and pharmacologically to 5-HT1 receptors in rodent brain membrane preparations, apart from a much-reduced affinity for 5-HT (160 nM compared to less than 5 nM in brain). Since NCB-20 cells also differ from rodent brain both qualitatively and quantitatively in their ganglioside composition, the effects of exogenously added gangliosides on the affinity of the 5-HT1 receptor for 5-HT were tested. Both GM1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside GQ1b produced a 10-fold increase in receptor affinity for [3H]5-HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC50 values for 5-HT-mediated elevation of intracellular cyclic AMP levels. GQ1b had the capacity to most dramatically enhance the potency of 5-HT in mediating increases in cyclic AMP levels. Gangliosides had no effect on the potency of DADLE or 3,4-dihydroxyphenylethylamine (dopamine)-mediated depression of cyclic AMP levels, suggesting some specificity for 5-HT. Our data are interpreted as implying a specific role for polysialogangliosides in modulating the affinity of the 5-HT1 receptor and the coupling of the 5-HT1 receptor-guanine nucleotide binding protein adenylate cyclase complex.
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PMID:Possible role of gangliosides in regulating an adenylate cyclase-linked 5-hydroxytryptamine (5-HT1) receptor. 299 94

Structure-activity studies with a number of adenosine derivatives and analogs, measuring their relaxant effects in a variety of smooth muscle systems, were conducted in the hope of obtaining indications of the possible involvement of adenylate cyclase in their mechanism of action. While it was confirmed that a C6 aminofunction is of importance for agonist activity, several compounds, in particular the relatively potent N6-hydroxylaminopurine ribonucleoside, were not antagonized by 8-p-sulfophenyltheophylline, indicating that some nucleosides cause smooth muscle relaxation by a mechanism other than adenosine receptor stimulation. Nucleosides not bearing a C6 aminofunction were essentially inactive in rabbit intestine but showed weak relaxant effects in bovine coronary artery; this may indicate a difference between the adenosine receptor systems in these tissues and the intracellular mechanisms of relaxation. Comparing the relative potencies of compounds such as adenosine, 2-chloroadenosine, 5'-(N-ethylcarboxamido)adenosine, and (-)N6-(R-phenylisopropyl)adenosine, which have been used widely to classify adenylate cyclase-coupled adenosine receptors, no uniform pattern became apparent among different smooth muscle systems used in this study and reported in the recent literature. Thus, we conclude that a classification of smooth muscle adenosine receptors according to criteria established for cyclase-coupled receptors may be inappropriate or misleading, particularly with respect to implications of adenylate cyclase involvement in the relaxant effects of adenosine and related nucleosides.
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PMID:Adenosine receptors in smooth muscle: structure-activity studies and the question of adenylate cyclase involvement in control of relaxation. 300 May 64

Our recent studies indicated that capping of T3, T4 and T8 surface antigens on human T lymphocytes is augmented by interaction of adenosine with a purinergic receptor. We suggested that the T-cell capping process was mediated by an adenylate cyclase-coupled purinergic receptor that resulted in the generation of cAMP and occupancy of cAMP receptors. The present study was undertaken to examine whether activation of adenylate cyclase in the absence of purinergic stimulation is sufficient to regulate surface antigen capping. Treatment of T lymphocytes with forskolin or cholera toxin caused activation of adenylate cyclase and occupancy of intracellular types I and II regulatory subunits of protein kinase by cAMP, as demonstrated by photoaffinity labeling with [8-3H]N3-cAMP. Such treatment augmented the rate of capping of the T3, T4, and T8 antigens, which resulted in a significant decrement in the elapsed time to half-maximal capping of each antigen. These observations support the proposition that the normal T-lymphocyte capping mechanism of both T3+, T4+ (inducer/helper) and T3+, T8+ (suppressor) subsets can be augmented by activation of adenylate cyclase.
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PMID:Role of adenylate cyclase in human T-lymphocyte surface antigen capping. 301 71

The biochemical mechanisms of adenylate cyclase desensitization in arginine vasopressin-responsive epithelial cells remain unclear. Preincubation of cultured rabbit renal cortical collecting tubular cells with arginine vasopressin leads to a 30-100% decline in arginine vasopressin-stimulated adenylate cyclase activity. This loss of adenylate cyclase activity is time- and arginine vasopressin concentration-dependent. Preincubation with arginine vasopressin does not result in significant changes in basal, NaF-, forskolin-, isoproterenol- or cholera toxin-stimulated adenylate cyclase activity. Preincubation of cells with chlorophenylthio-cAMP, forskolin, and cholera toxin does not result in loss of arginine vasopressin-stimulated adenylate cyclase activity. Since products of cyclo-oxygenase inhibit arginine vasopressin action, cells were preincubated with indomethacin. Arginine vasopressin-induced adenylate cyclase desensitization is not reversed by indomethacin. By contrast, incubation with pertussis toxin prevents arginine vasopressin-induced adenylate cycle desensitization. These data demonstrate that arginine vasopressin induces homologous desensitization in membranes from cultured rabbit cortical collecting tubular cells and suggest that this desensitization is mediated, at least in part, by pertussis toxin substrate. These observations provide a unifying mechanism for desensitization of adenylate cyclase-coupled hormone receptors.
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PMID:Pertussis toxin prevents homologous desensitization of adenylate cyclase in cultured renal epithelial cells. 308 Apr 28

The human gastric epithelial cell line HGT-1 possesses adenylate cyclase-coupled histamine H2 receptors. To test the cellular homogeneity or heterogeneity with respect to these receptors, we have isolated 7 clones from the HGT-1 line and studied their basal and histamine-stimulated adenylate cyclase activities. Basal adenylate cyclase activities of the clones did not differ significantly, nor did 10 mM NaF- nor 0.1 mM Gpp(NH)p-stimulated activities. However, histamine stimulation of adenylate cyclase varied among clones from 1.9 fold to 5.4 fold basal activity. The EC50 values, determined in 3 clones, were not significantly different. These findings support the heterogeneity of histamine responsiveness of the human gastric cell line HGT-1. In addition, they suggest that highly histamine-responsive clones may be useful models to study the gastric histamine H2-receptor and its specific antagonists in the human.
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PMID:Highly histamine-responsive clones from the human gastric adenocarcinoma cell line HGT-1. 370 47

In an attempt to characterize the adenylate cyclase-coupled alpha-adrenoceptors of human fat cells the effects of various alpha-adrenergic agonists and antagonists were examined in the presence of 0.05 mmol/l of propranolol. The order of agonist potencies with respect to alpha-adrenergic inhibition was (-)-adrenaline greater than alpha-methyl-(-)-noradrenaline greater than (-)-phenylephrine with half-maximal inhibition occurring at 2 mumol/l of (-)-adrenaline and 7 mumol/l of alpha-methyl-(-)-noradrenaline respectively. The inhibition of adenylate cyclase induced by 0.05 mmol/l of (-)-adrenaline was reversed by the alpha-blocking agents yohimbine and prazosin, with the alpha 2-site-directed antagonist yohimbine being more than 100-times more potent than prazosin which is more active at alpha 1-sites. The results show that the cyclase-coupled alpha-adrenoceptors of human fat cells, which probably represent the physiologically relevant target of antilipolytic catecholamine effects, display characteristic features of the alpha 2-adrenoceptor subtype.
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PMID:Adrenoceptor of the alpha 2-subtype mediating inhibition of the human fat cell adenylate cyclase. 611 51

The guanine nucleotide regulatory protein(s) regulates both adenylate cyclase activity and the affinity of adenylate cyclase-coupled receptors for hormones or agonist drugs. Cholera toxin catalyzes the covalent modification of the nucleotide regulatory protein of adenylate cyclase systems. Incubation of frog erythrocyte membranes with cholera toxin and NAD+ did not substantially alter the dose dependency for guanine nucleotide activation of adenylate cyclase activity. In contrast, toxin treated membranes demonstrated a 10 fold increase in the concentrations of guanine nucleotide required for a half maximal effect in regulating beta-adrenergic receptor affinity for the agonist (+/-) [3H]hydroxybenzylisoproterenol. The data emphasize the bifunctional nature of the guanine nucleotide regulatory protein and suggest that distinct structural domains of the guanine nucleotide regulatory protein may mediate the distinct regulatory effects on adenylate cyclase and receptor affinity for agonists.
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PMID:Differential effects of cholera toxin on guanine nucleotide regulation of beta-adrenergic agonist high affinity binding and adenylate cyclase activation in frog erythrocyte membranes. 612 32

Cultured NCB-20 mouse neuroblastoma X Chinese hamster brain clonal hybrid cells express an adenylate cyclase-coupled receptor for serotonin (5HT) which corresponds pharmacologically to the 5HT1 receptor in whole brain, except for its much lower affinity for serotonin. Studies showed that the affinity of the NCB-20 receptor could be increased to near that of the whole brain receptor and the potency of 5HT in elevating cyclic AMP levels increased by pre-incubating NCB-20 cells for at least 3 hours with submicromolar concentrations of brain gangliosides. Tetrasialoganglioside (GQ1b) was found to be the most potent ganglioside tested, producing a ten-fold increase in affinity. However, the actual 5HT binding site is a protein and we have obtained no evidence that serotonin binds directly to gangliosides at the concentrations at which it labels the receptor. The receptor-mediated inhibition of adenylate cyclase by biogenic amines such as dopamine and clonidine through dopamine (D2) and alpha-adrenoreceptors was unaffected by pre-incubation of the NCB-20 cells with gangliosides. Enkephalin was also found to acutely supress both the ability of 5HT to stimulate adenylate cyclase activity and the synthesis of polysialogangliosides in NCB-20 cells. After 6 hours of exposure, the cells became tolerant to enkephalin and after 36 hours the cells became supersensitive to 5HT in terms of adenylate cyclase activation and 5HT binding. The affinity of the receptor for 5HT increased the same 10-fold magnitude as achieved by GQ1b pre-incubation in comparison with untreated cells. This increase in receptor affinity appeared to coincide chronologically with the increase in ganglioside synthesis observed in enkephalin tolerant cells, further suggesting an important role of polysialogangliosides in the function of the serotonin (5HT1) receptor.
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PMID:Gangliosides as modulators of the coupling of neurotransmitters to adenylate cyclase. 614 53

A decrease in isoproterenol-stimulated adenylate cyclase activity has been shown in various tissues of hypertensive rats, a finding often associated with decreased beta-adrenoceptor number. The present study was undertaken to investigate whether adenylate cyclase stimulation by other hormones is similarly affected. Adenylate cyclase activity in cerebral microvessels under control conditions and following stimulation by isoproterenol, prostaglandin E1, and the adenosine analog 5'-(N-ethylcarboxamide)-adenosine (NECA) was significantly diminished in deoxycorticosterone acetate (DOCA)-hypertensive rats as compared with control rats, as was adenylate cyclase stimulation by GTP, fluoride, and forskolin. Similar results were obtained in cardiac ventricular membranes, apart from the fact that NECA did not influence adenylate cyclase activity in the heart, either in normotensive or in hypertensive rats. In both the heart preparation and the microvessel preparation, beta-adrenoceptor numbers were reduced in DOCA-hypertensive rats. Because the adenylate cyclase data also pointed to functional alteration at the guanine nucleotide regulatory site of the adenylate cyclase complex, the influence of DOCA hypertension on receptor-adenylate cyclase coupling was investigated by competition studies for beta-adrenoceptor binding. In ventricular membranes prepared from DOCA-hypertensive rats, the isoproterenol competition curve for [125I]iodocyanopindolol binding was only slightly altered in the presence of guanylyl imidodiphosphate (50 microM), in contrast to normotensive control rats, in which it was shifted to the right and became significantly steeper. These results are suggestive of decreased guanine nucleotide sensitivity of adenylate cyclase-coupled receptors in DOCA hypertension.
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PMID:The cardiac and brain microvessel adenylate cyclase system in deoxycorticosterone acetate-hypertensive rats. 620 Jul 23


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