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)

For a variety of ligand states, adenylate cyclase activity in the presence of Mn2+ was greater than with Mg2+. Trypsin treatment of intact hepatocytes, under conditions which destroy cell surface glucagon receptors, led to a first order loss of glucagon-stimulated adenylate cyclase activity in isolated membranes assayed in the presence of Mn2+ whether or not GTP (100 microM) was present in the assays. Arrhenius plots of basal activity exhibited a break at around 22 degrees C, those with NaF were linear and those with glucagon +/- GTP (100 microM) were biphasic with a break at around 28 degrees C. It is suggested that Mn2+ perturbs the coupling interaction between the glucagon receptor and catalytic unit of adenylate cyclase at the level of the guanine nucleotide regulatory protein. This appears to take the form of Mn2+ preventing GTP from initiating glucagon's activation of adenylate cyclase through a collision coupling mechanism.
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PMID:Mechanism of glucagon activation of adenylate cyclase in the presence of Mn2+. 630 47

The effects of trypsin treatment on VIP binding to rat intestinal epithelial cell membranes were examined. The decrease in specific binding of [125I]VIP is dependent on the amount of trypsin used and digestion time. Specific binding decreases by 50% after 8 min with 20 micrograms/ml trypsin. Trypsin is active in the 1-100 micrograms/ml concentration range (ED50 approximately equal to 5 micrograms/ml). Non-specific binding is unaltered by the enzyme. The effect of trypsin is abolished by trypsin inhibitor. Scatchard analysis of VIP binding reveals two types of binding sites: sites I characterized by a high affinity, a low capacity and a high sensitivity to low trypsin levels (1-5 micrograms/ml); sites II characterized by a low affinity, a high capacity, resistant to low trypsin levels (1-5 micrograms/ml) but sensitive to a high trypsin level (20 micrograms/ml). Trypsin decreases the binding capacity by lowering the site number without altering their affinity. Sites not destroyed by trypsin retain their functional characteristics: KD, sensitivity to GTP and coupling with adenylate cyclase. It is concluded that sites I and II are proteins with different structures and/or differently localized in the membrane.
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PMID:Intestinal VIP receptors: differential effect of trypsin on the high and low affinity binding sites. 631 49

The molecular and species specificity of glucocorticoid suppression of corticosteroidogenesis was investigated in isolated adrenocortical cells. Trypsin-isolated cells from male rat, domestic fowl and bovine adrenal glands were incubated with or without steroidogenic agents and with or without steroids. Glucocorticoids were measured by radioimmunoassay or fluorometric assay after 1-2 h incubation. Glucocorticoids suppressed ACTH-induced steroidogenesis of isolated rat cells with the following relative potencies: corticosterone greater than cortisol = cortisone greater than dexamethasone. The mineralocorticoid, aldosterone did not affect steroidogenesis. Suppression by glucocorticoids was acute (within 1-2 h), and varied directly with the glucocorticoid concentration. Testosterone also suppressed ACTH-induced steroidogenesis. Glucocorticoid-type steroids have equivalent suppressive potencies, thus suggesting that these steroids may induce suppression at least partly by a common mechanism. Although corticosterone caused the greatest suppression, testosterone was more potent. The steroid specificity of suppression of cyclic AMP (cAMP)-induced and ACTH-induced steroidogenesis were similar, suggesting that suppression is not solely the result of interference with ACTH receptor function or the induction of adenylate cyclase activity. Exogenous glucocorticoids also suppressed ACTH-induced steroidogenesis of cells isolated from domestic fowl and beef adrenal glands, thus suggesting that this observed suppression may be a general mechanism of adrenocortical cell autoregulation.
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PMID:Steroid control of steroidogenesis in isolated adrenocortical cells: molecular and species specificity. 632 May 2

Trypsin, chymotrypsin, and papain stimulate basal adenylate cyclase activity in bovine thyroid plasma membranes in a dose-related, albeit biphasic, fashion. Each of the proteases enhanced TSH-stimulated adenylate cyclase activity over basal activity. The proteases also enhanced GTP-, guanosine 5'-(beta, gamma-imidotriphosphate)-, prostaglandin E1-, and cholera toxin-stimulated adenylate cyclase to varying degrees. Fluoride-stimulated activity was enhanced by chymotrypsin and papain, but not by trypsin. When Mn++ was substituted for Mg++ in the adenylate cyclase assay, no stimulation by the proteases were observed. To see if endogenous membrane proteases are required for optimal thyroid adenylate cyclase response to TSH and other stimulators, studies were performed using the protease inhibitors tosylamide 2-phenylethyl-chloromethyl ketone (TPCK) and p-tosyl-L-arginine methyl ester (TAME), inhibitors of chymotrypsin and trypsin, respectively. TPCK (0.15 mM) had no effect on basal adenylate cyclase activity, but did inhibit TSH-, trypsin-, and chymotrypsin-stimulated activities by approximately 90%. Guanosine 5'-(beta, gamma-imido) triphosphate- as well as cholera toxin-stimulated activities were inhibited by approximately 50%, whereas prostaglandin E1- and fluoride-stimulated activities were inhibited by approximately 25%. TAME (6 mM) produced similar results, except that no effect on fluoride activity was seen, while basal activity was inhibited by approximately 20%. Thus, various serine proteases augment both basal and hormone-stimulated adenylate cyclase in bovine thyroid. Since both trypsin- and chymotrypsin-stimulated as well as TSH-induced enzyme activities were inhibited by TPCK and TAME, it would appear that augmentation of thyroid adenylate cyclase activity may, in part, result from stimulation of endogenous proteases.
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PMID:Effects of proteolytic enzymes and protease inhibitors on bovine thyroid adenylate cyclase activity. 633 11

The associations of the components of eucaryotic adenylate cyclase are still poorly characterized. Enzyme activity is, however, thought to depend upon subunit conformations and states of association. Estimates of adenylate cyclase sizes corresponding to given levels of activity may thus give clues as to how the enzyme functions. Studying the rat brain enzyme, we found that samples protected from proteolysis throughout the fractionation procedure yielded, upon Lubrol solubilization, a soluble protein complex of 9.1S sedimentation coefficient and 11.5-nm Stokes radius. These values are much larger than those previously reported. The soluble enzyme specific activity, but not its size, was dependent upon the various effectors preincubated with the membranes. Proteolysis is known to first activate and then decrease adenylate cyclase activity. Proteolysis of the brain samples, whether due to trypsin or to endogeneous proteases, decreased the adenylate cyclase s value, Stokes radius, and specific activity altogether. The magnitude of the shifts depended upon the nature of the enzyme effector preincubated with the membranes. We recently showed that some brain membrane proteins can be ADP-ribosylated by cholera toxin, concomitantly with adenylate cyclase activation [Berthillier, G., d'-Alayer, J., & Monneron, A. (1982) Biochem. Biophys. Res. Commun. 109, 297-304]. Trypsin treatment of such samples led to a quick degradation of the labeled polypeptides and especially of the Mr 47000 protein. This Lubrol soluble protein is likely to be the brain G/F stimulatory subunit.
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PMID:Structure of brain adenylate cyclase: proteolysis-dependent modifications. 661 11

1. The effect of various proteolytic enzymes was assayed on the adenylate cyclase activity in purified brain membrane preparations from the insect Ceratitis capitata. Trypsin, chymotrypsin, papain, thermolysin, elastase, subtilisin and prot. XIV were examined. 2. Trypsin treatment, at 37 degrees C, decreased the adenylate cyclase activity even in the presence of GppNHp that protects the activity from the thermal inactivation. 3. Residual basal, GppNHp- and F(-)-stimulated activities were similar when membrane preparations were preincubated either in the presence or in the absence of GppNHp and F-. 4. All proteolytic activities assayed on the brain membrane preparations, excepting papain, exerted an inhibition of adenylate cyclase in basal conditions. 5. The inhibition was stronger in the presence of F- than in the presence of other regulators. 6. Papain showed also a notable inhibition of adenylate cyclase in the presence of F-. 7. Phospholipase A2 treatment decreased both basal and stimulated activity; however, F(-)-sensitive activity was less affected than basal and GppNHp-sensitive activity. F(-)-stimulated activity was less affected by phospholipase A2 than either basal or GppNHp-stimulated activities. 8. Phospholipids are, then, essential for the highest basal activity, although the relationship between catalytic and nucleotide-regulatory components was unaffected by this treatment.
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PMID:Effect of proteolytic and lipolytic enzymes on the adenylate cyclase activity from brain membranes of Ceratitis capitata. 675 15

The modulation of the luteinizing hormone (LH) induction of cholesterol side chain cleavage (CSCC) enzyme in immature rat Leydig cells was studied using rat Sertoli cell-conditioned medium (SCCM), which stimulates short-term endogenous steroid production. Luteinizing hormone increased the CSCC enzyme activity 10-fold in cells cultured for 7 days in the absence of hormones. This enzyme induction was abolished almost completely in the presence of SCCM. The inhibition was dose dependent (half-maximal effect at 5 mg protein/l) and paralleled by a decrease in the amount of cytochrome P-450scc (P-450scc) enzyme. There were no indications for loss of cell viability. The inhibitory action of SCCM could be localized at the level of adenylate cyclase activation and at steps beyond cyclic adenosine monophosphate production. The inhibition was not specific for Sertoli cell products because conditioned media from different cell lines and media from isolated rat hepatocytes displayed similar effects. Trypsin treatment of SCCM destroyed the activity whereas the bioactivity could resist heating for 5 min at 100 degrees C. Generally occurring (growth) factors, such as epidermal growth factor or tumor necrosis factor alpha, may have contributed to the observed inhibitory effects of SCCM. These inhibitory effects of Sertoli cell products in vitro are in contrast to stimulatory effects of Sertoli cells on Leydig cell steroidogenesis in vivo after FSH administration.
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PMID:Inhibition of the luteinizing hormone-dependent induction of cholesterol side chain cleavage enzyme in immature rat Leydig cells by Sertoli cell products. 774 7

Cholera toxin is an ubiquitous activator of intracellular adenylate cyclase and is divided in two major components: A and B. The B-component consists of several subunits that specifically bind to the external cell membrane. The receptor for the toxin, the GM1 ganglioside, is concentrated in nervous tissues. The B subunit of the cholera toxin, conjugated to different molecules (i.e., choleragenoid) is therefore a sensitive anatomical tracer and has been used to detect the presence of GM1 in mammalian tissues. Using choleragenoid, unlabeled and labeled with FITC, we have determined the distribution of the GM1 ganglioside in the vestibular system of the chinchilla. Vestibular tissues were fixed in 4% paraformaldehyde in phosphate buffer, decalcified in 10% EDTA and prepared as either whole-mount, surface-preparations, or for radial cryosections. Positive control tissue consisted of binding to normal brain tissues. Negative controls consisted of several treatments: masking of the GM1 receptors with unlabeled choleragenoid, tissue extraction of GM1 using ethanol, and preabsorbing the choleragenoid with bovine GM1. In addition, to exclude staining of glycoproteins that may have a carbohydrate structure similar to GM1, tissues were digested with trypsin prior to choleragenoid exposure. In the vestibular system, a strongly positive reaction was observed in: the sensory stereocilia and supporting cells of the maculae and cristae, epithelial cells of the planum semilunatum, and polygonal cells of the semicircular canal. Positive but less strong reactivity was observed in the sensory cell body of maculae and cristae, nerve fibers, epithelial cells of utricle and ampulla walls and flattened epithelial cells of the semicircular canals. No reactivity was present in the supporting connective tissue cells and fibrils, blood vessels, gelatinous cupula of the cristae ampullaris and statoconial membranes. Brain tissue showed strong choleragenoid reactivity. The negative controls showed no or greatly reduced reactivity to choleragenoid. Trypsin digestion did not decrease reactivity to choleragenoid.
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PMID:Localization of the GM1 ganglioside in the vestibular system using cholera toxin. 843 86

Adenylate cyclase in synaptic plasma membranes from rat brain is activated by ?-chymotrypsin or trypsin. These proteases also activate adenylate cyclase reconstituted from the catalytic subunit of adenylate cyclase and the partially purified fraction of the GTP-binding proteins containing both the stimulatory and inhibitory GTP-binding proteins. Properties of the activation of reconstituted adenylate cyclase by the proteases are as follows. (1) The proteases do not directly activate the catalytic subunit. However, the pre-treatment of the partially purified GTP-binding proteins with ?-chymotrypsin (100 ?g/ml) increases the subsequently reconstituted cyclase activity at least 3-fold. Trypsin (10-30 ?g/ml) much more weakly enhances the cyclase activity. (2) ?-Chymotrypsin and trypsin synergistically activate the cyclase. (3) Trypsin but not ?-chymotrypsin no longer activates the cyclase when the purified stimulatory GTP-binding protein (Gs) replaces the partially purified GTP-binding proteins. (4) The stimulatory effects of ?-chymotrypsin and trypsin on the cyclase activity are little or slight unless 5?-guanylylimidodiphosphate (Gpp(NH)p) is present in the reconstitution. (5) The purified ??-subunits of the GTP-binding proteins markedly inhibit adenylate cyclase. This inhibition is nearly completely attenuated by treating the ??-subunits with ?-chymotrypsin (> 10 ?g/ml). (6) Trypsin (1-10 ?g/ml) inactivates the GTPase of the ?-subunit of the inhibitory GTP-binding protein (Gi). This inactivation of the GTPase seems to correlate with the activation of the reconstituted adenylate cyclase by trypsin. We conclude that two distinct protein components are involved in the activation of adenylate cyclase by ?-chymotrypsin and trypsin. One component sensitive to ?-chymotrypsin is probably the ??-subunits of the GTP-binding proteins. The other component sensitive to trypsin may be the ?-subunit of Gi.
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PMID:Activation of rat brain adenylate cyclase by proteases: involvement of distinct protein components in the activation by ?-chymotrypsin and trypsin. 2050 Dec 51


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