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)

ADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8.
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PMID:Competitive inhibition by lithium and hydrogen ions of the effect of calcium on the aggregation of rabbit platelets. 1 92

Sarcolemma was isolated by fractionation of salt-extracted particles on two consecutive sucrose density gradients. Salt extraction of homogenates, rather than of washed particles, was found to preserve the activities of adenylate cyclase and ouabain-sensitive (Na+,-K+)-ATPase in the isolated sarcolemmal membranes. Purified sarcolemma contained substantial adenylate cyclase and guanylate cyclase activities that were stimulable by beta-adrenergic and muscarinic agonists, respectively. Significant ouabain-sensitive (Na+, K+)-ATPase activity as well as putative digitalis receptor activity was also present in sarcolemma. Cyclic nucleotide phosphodiesterases of sarcolemma, both cAMP- and cGMP-dependent, displayed positive cooperativity of substrate interactions; Ca2+ ions were found to increase the activity of the GMP-dependent enzyme.
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PMID:Isolation and enzymatic characterization of guinea pig cardiac sarcolemma. 2 1

Salmonellae, shigellae and some Escherichia coli must invade the intestinal epithelial cell and multiply within the mucosa to cause disease. Although the bacterial cell most likely possesses several properties essential to this invasive ability, the nature of the cell envelope complex is at present the only characteristic which has been implicated in this process. While a number of pathophysiological events result from invasion, some of our recent efforts have concerned the site and mechanism of intestinal fluid loss in salmonellosis and shigellosis. In both these disorders, bacterial invasion of the colonic mucosa, associated with an acute inflammatory reaction and mucosal damage, is regularly seen and colonic salt and water transport is abnormal. These defects may account for mild diarrhoea in salmonellosis and the dysenteric stools of shigellosis. However, in salmonella-infected animals with severe watery diarrhoea and in shigella-infected animals with diarrhoea alone or in combination with dysentery, the jejunum is in a net secretory state. This secretion occurs in the absence of bacterial invasion or morphological abnormalities. Thus, the diarrhoea caused by invasive bacteria may result from the inability of the colon to reabsorb the increased volume of fluid entering it from the small intestine. Although colonic mucosal damage is a feature of invasive-type diarrhoeas, the permeability of both the colon and small intestine to small molecules, mannitol and erythritol, is not altered. Thus intestinal fluid loss cannot be ascribed to transudation. In addition, the results of our Ussing chamber experiments, employing salmonella-infected rabbit ileum, reveal that salt and water secretion is an active process. Since secretion occurs in the jejunum in the absence of bacterial invasion, this might suggest the participation of an enterotoxin. Shigella dysenteriae I is the best-studied invasive organism in which an enterotoxin has been found, yet mutant strains which do not invade but retain the ability to elaborate enterotoxin fail to cause disease in either monkeys or man. Thus, the physiological relevance of Shiga enterotoxin and the mechanism of jejunal secretion in these disorders remain unclear. Recent data suggest that invasive enteropathogens, like the enterotoxin-producing bacteria, activate the mucosal adenylate cyclase-cyclic AMP system and that this activation may play a role in intestinal fluid secretion.
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PMID:Studies on the pathogenesis of enteric infections caused by invasive bacteria. 6 46

A vasopressin resistant urinary concentrating defect has been described in patients receiving lithium salt for affective disorders. For the pathogenic mechanism of the concentrating defect it has been postulated that lithium inhibits the vasopressin-dependent cyclic AMP system. However, the results of indirect studies on the lithium effect are equivocal. Therefore, the effect of lithium specifically on the vasopressin-dependent cyclic AMP system was investigated in rat renal medulla. The increase of cyclic AMP concentration by vasopressin was inhibited by lithium. But lithium had no effect on the PTH-dependent cyclic AMP concentration in renal cortical slices. Regardless of magnesium concentrations from 0-10 mM in the incubation media, 10 mM lithium had no moeasurable effect on the vasopressin-dependent adenylate cyclase of rat renal medulla. However, 10 mM lithium augmented the cyclic AMP-phosphodiesterase activity in renal medulla in the high Km system. These results suggest that lithium inhibits the vasopressin-dependent cyclic AMP concentration in renal medulla via the augmentation of its catabolism, rather than via the inhibition of cyclic AMP generation.
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PMID:Effects of lithium on vasopressin-dependent cyclic AMP in rat renal medulla. 16 28

Adenosine triphosphatase (ATPase) activity in erythrocyte membranes from patients with Duchenne dystrophy was inhibited by ouabain less than in normal individuals in assay systems containing high or low contents of salt. Epinephrine and cyclic adenosine monophosphate increased total ATPase activity in all samples, and epinephrine restored ouabain sensitivity to the Duchenne membranes. Basal adenyl cyclase activity in about twice that of controls. Epinephrine stimulated adenyl cyclase activity of normal membranes two to three times, but did not stimulate the enzyme in Duchenne membranes. These differences may reflect a genetic abnormality of the membrane.
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PMID:Biochemical abnormalities of erythrocyte membranes in Duchenne dystrophy. Adenosine triphosphatase and adenyl cyclase. 18 Sep 37

Cultured thyroid cells accumulate the lipophilic cation triphenylmethylphosphonium, indicating that there is an electrical potential (interior negative) across the plasma membrane. Thyrotropin stimulates the uptake of the lipophilic cation 3-fold, and the proton conductor carbonylcyanide-m-chlorophenylhydrazone causes efflux of triphenylmethylphosphonium accumulated in the presence or absence of thyrotropin. The stimulatory effect of thyrotropin on triphenylmethylphosphonium accumulation is not mimicked by human chorionic gonadotropin, a glycoprotein hormone with a similar structure whose target organ is not the thyroid, and the effect is abolished if the thyrotropin-receptor activity of the cells is destroyed by treatment with trypsin. Analogous effects are observed with thyroid plasma membrane vesicles which are essentially devoid of mitochondrial and soluble enzyme activities. Triphenylmethylphosphonium uptake and stimulation by thyrotropin occurs when NaCl, KCl, or Tris.HCl concentration gradients are artifically imposed across the vesicle membrane ([salt](out) > [salt](in)). It seems likely, therefore, that triphenylmethylphosphonium uptake is driven by a chloride diffusion potential (interior negative) and that thyrotropin either increases the permeability of the membrane to anions or decreases its permeability to cations. Thyrotropin-stimulated triphenylmethylphosphonium uptake in the vesicle preparations reaches a quasi steady-state within 3 min; in contrast, thyrotropin-stimulated adenylate cyclase activity is negligible during this period of time, becomes measurable after about 4 min, and is optimal after 12-15 min. Thus, a primary mode of action of thyrotropin on the thyroid cell may be an alteration in the electrical potential across the plasma membrane. The relevance of this observation to the mechanism of action of other glycoprotein hormones, certain bacterial toxins, and interferon is discussed.
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PMID:Effects of thyrotropin on the thyroid cell membrane: hyperpolarization induced by hormone-receptor interaction. 19 88

Previous work had demonstrated the coupling of a beta-adrenergic receptor on an erythrocyte with the adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of a tissue culture cell when the two cells were fused by Sendai virus. The validity of this finding for animal tissues in general, for membrane preparations, and for peptide hormone receptors could hitherto not be assessed. Available fusion procedures worked efficiently only with certain intact cells from tissue culture and with erythrocytes. In the present work a membrane fusion method was developed that causes the transfer of the glucagon receptor from purified rat liver membranes to Friend erythroleukemia cells; even direct transfer to a membrane fraction prepared from Friend cells became feasible. It can therefore be concluded that a peptide hormone receptor in a normal tissue membrane has properties similar to those demonstrated for a beta-adrenergic receptor in an erythrocyte: it exists in the membrane as a dissociable independent unit that can readily couple with the adenylate cyclase of a foreign cell. The efficiency of the membrane fusion procedure is due to the combined action of polyethylene glycol, phospholipids, stearylamine, and ATP in a salt medium. The method promises to be applicable to membranes of various cells and tissues, and it can probably be used to analyze hormone receptors and adenylate cyclase systems in states of malfunction by transfer to their respective counterpart in a normal cell membrane. Studies in biochemical hybridization of membrane components need not be limited to hormone activation of adenylate cyclase. With the aid of the membrane fusion method, this approach could be applied to any dissociable multicomponent system in biological membranes.
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PMID:Transfer of glucagon receptor from liver membranes to a foreign adenylate cyclase by a membrane fusion procedure. 22 Jun 8

The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in beta-adrenergic receptors. The specific binding of the beta-adrenergic antagonist, 125I-iodohydroxybenzylpindolol, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer beta-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 +/- 19 to 49 +/- 5 fmol/mg protein for DOCA-salt hypertension and from 110 +/- 18 to 75 +/- 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged.
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PMID:Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats. 22 57

A strongly fluorescent 5-dimethylamino-1-naphthalene sulfonate (dansyl) derivative of bovine thyrotropin has been prepared. The dye-conjugated hormone is bioactive and shares, essentially unchanged, the membrane binding and adenylate cyclase stimulatory activities of the native hormone. Binding of 125I-labeled dansyl-thyrotropin to thyroid plasma membranes is sensitive to inhibition by gangliosides and, as is the case for the binding of 125I-thyrotropin, galactosyl-N-acetylgalactosaminyl[N-acetylneuraminyl-N-acetylneuraminyl]-galactosylglucosylceramide (GDIb) is the most potent binding inhibitor. Gangliosides interact with dansyl-thyrotropin, causing a large increase of the quantum yield and a 5- to 10-nm blue shift of the emission maximum of the hormone-bound naphthalene chromophore; gangliosides cause no change in the fluorescent properties of the free dye. The fluorescence enhancement caused by gangliosides can be specifically reversed by unlabeled thyrotropin. The effect of gangliosides on dansyl-thyrotropin fluorescence is strongly salt-dependent; salts cannot, however, reverse the formation of the dansyl-thyrotropin.ganglioside complex once it has formed. The salt data suggest that the association of the ganglioside with dansyl-thyrotropin is dominated by electrostatic interactions, but that salt-independent, short range interactions, most likely hydrophobic, dominate the dissociation of the dansyl-thyrotropin-ganglioside adduct. Sucrose gradient centrifugation, ultracentrifugation, and fluorescence polarization data indicate that the gangliosides are micellar in nature under the conditions of these experiments. Acid titration of dansyl-thyrotropin causes a marked quenching of dansyl fluorescence which in part reflects dissociation of the hormone into its constituent alpha and beta subunits. In the presence of GDIb, but not N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GDIa), pH-dependent quenching and subunit dissociation are essentially eliminated. Circular dichroism results and fluorescence polarization studies support the interpretation that the ganglioside interaction causes a conformational change in the thyrotropin molecule. The acid titration data together with differences in the ability of gangliosides to influence the tyrosine fluorescence of the thyrotropin molecule indicate that different gangliosides induce different conformational perturbations in the thyrotropin molecule.
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PMID:Dansylated thyrotropin as a probe of hormone-receptor interactions. 22 19

The effect of molybdate on adenylate cyclase (EC 4.6.1.1) in rat liver plasma membranes has been examined. The apparent K alpha for molybdate activation of the enzyme is 4.5 mM, and maximal, 7-fold stimulation is achieved at 50 mM. The observed increase in cAMP formation in the adenylate cyclase assay is not due to: (a) an inhibition of ATP hydrolysis; (b) a molybdate-catalyzed conversion of ATP to cAMP; (c) an inhibition of cAMP hydrolysis; or (d) an artifact in the isolation of cAMP formed in the reaction. Molybdate activation of adenylate cyclase is a general phenomenon exhibited by the enzyme in brain, cardiac, and renal tissue homogenates and in erythrocyte ghosts. However, like fluoride and guanyl-5'-yl imidodiphosphate (Gpp(NH)p), molybdate does not activate the soluble rat testicular adenylate cyclase. Molybdate is a reversible activator of adenylate cyclase. Activation is not due to an increase in ionic strength and is independent of the salt used to introduce molybdate. Molybdate does not activate adenylate cyclase previously stimulated with Gpp(NH)p or fluoride. At concentration greater than 20 mM, molybdate inhibits fluoride-stimulated adenylate cyclase, and at concentrations greater than 100 mM, molybdate stimulation of basal adenylate cyclase activity is diminished.
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PMID:Activation of adenylate cyclase by molybdate. 45 57


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