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)

Methods have been developed for the isolation on a semi-micro scale of a plasma membrane-enriched fraction from rat islets of Langerhans. An important feature of these experiments is the use of 125I-labeled wheat germ agglutinin as a specific probe for plasma membrane-containing fractions. The partly purified plasma membrane fraction had a density in sucrose of about 1.10 and was enriched in the activities of 5'-nucleotidase, alkaline phosphatase, sodium-potassium, and magnesium-dependent ATPase and adenylate cyclase. It contained only very low levels of acid phosphatase, cytochrome c oxidase, insulin, and RNA. Further purification was hampered by the relatively small amounts of fresh plasma membrane material that could be obtained from 16-24 rats in each experiment. When islets were prelabeled with radioactive fucose, the plasma membrane-enriched fraction contained radioactivity at a four- to fivefold higher specific acivity than the whole islet homogenate. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis of plasma membrane-enriched fractions pooled from several experiments revealed a distinctive pattern of protein bands as compared with other less pure fractions. With respect to rapidity, apparent specificity, and easy reversibility of the labeling of the plasma membrane fraction, 125I-wheat germ agglutinin provides a highly useful tool for the detection of microgram quantities of plasma membrane components which should be applicable to many other systems as well.
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PMID:Preparation and characterization of plasma membrane-enriched fractions from rat pancreatic islets. 79 56

Homeostasis of the internal environment in mammals is accomplished by a series of feedback mechanisms in a variety of tissues. Homeostasis of cell structure and function during marked changes in the environment is equally important. Both types of homeostasis are dependent on adjustments in endocrine function and changes in enzyme activity. In some instances the intracellular servomechanisms required for homeostasis match in vigor and range the perturbations of the external environment. The regulation of cell metabolism is accomplished by enzymatic, membranous and genetic mechanisms. Most peptide hormones act by combining with a specific receptor in the membrane of sensitive cells, which activates adenyl cyclase to produce cyclic AMP which in turn has selective second messenger functions. Insulin and somatotropin appear to be exceptions and may act via cyclic GMP. Steroid hormones, on the other hand, pass through the cell membrane and combine with a specific receptor protein in the cytoplasm of sensitive cells. This receptor then serves as a transport system for movement of the hormone to the nucleus where it stimulates specific protein synthesis. Nutritional effects on enzyme synthesis are partially direct and partially mediated by the endocrine system. Trace nutrients, especially the fat-soluble vitamins, appear to act directly to modify specific protein syntheses, whereas the bulkier constituents of the diet (carbohydrate, fat protein) exert their effects principally through altered rates of secretion of insulin, glucagon, and the glucocortioids. Protein-calorie malnutrition is the result of a massive assault on homeostatic and adaptive mechanisms designed to conserve nutrients and preserve life. The pathogenesis of marasmus and kwashiorkor is discussed in the light of these adaptive mechanisms.
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PMID:Introductory remarks: nutrient, hormone, enzyme interactions. 80 21

Rats treated chronically with dopamine receptor blockers were found to have an increase in striatal 3H-dopamine binding and adenylate cyclase activity as manifestations of receptor supersensitivity. Both the increase in binding and in adenylate cyclase activity were reversed by chronic 1-dopa treatment, presumably by increasing the supply of specific ligand (dopamine). The use of deliberate receptor sensitivity manipulation may be useful as a treatment for conditions involving disturbances in receptor sensitivity such as tardive dyskinesia and insulin resistant diabetes.
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PMID:Reversal of two manifestations of dopamine receptor supersensitivity by administration of L-dopa. 84 96

The hemodynamic responses of normal subjects to intravenous injections of tolbutamide, 250 mg., and 1,000 mg., were assessed by measurements of serial systolic time intervals. Analysis of results, compared to saline control, revealed evidence of minor inotropic effects during the period five to 10 minutes after infusion. Small but statistically significant (p less than 0.05) decreases in pre-ejection phase and electromechanical systole were noted. The time response of these changes did not correlate with dose of blood level of tolbutamide, and appeared to coincide with peak insulin levels. No inotropic or chronotropic effects were seen during the first four minutes after infusion, suggesting that the myocardial adenyl cyclase-stimulating properties of the drug, previously demonstrated in vitro, are not significant in intact man. The minor late inotropic effects are of doubtful clinical significance, and cannot be invoked to explain the reported increased cardiovascular mortality of patients treated with tolbutamide.
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PMID:Inotropic effects of tolbutamide in man. 109 Jan 33

To determine whether somatostatin inhibits glucagon secretion directly at the pancreatic level and to study quantitatively the relative effects of somatostatin on glucagon and insulin secretion, the effects of various concentrations of somatostatin on glucagon and insulin release from the in vitro perfused rat pancreas in response to arginine (14.2 mM), isoproterenol (2 mg/ml) and theophylline (10 MM) were studied. Glucagon and insulin responses to arginine were progressively inhibited by somatostatin over a concentration range from 0.1-100 ng/ml. At all doses, somatostatin caused greater inhibition of glucagon secretion than of insulin secretion. Approximately 4 ng/ml somatostatin reduced glucagon responses 50%, whereas 90 ng/ml was required to produce comparable inhibition of insulin responses. Glucagon responses to isoproterenol, an activator of adenylate cyclase, and to theophylline, a phosphodiesterase inhibitor, were completely abolished by 100 ng/ml somatostatin. Isoproterenol did cause insulin release in this system, but insulin responses to theophylline were diminished by somatostatin. The present studies thus indicate that somatostatin is a potent inhibitor of both glucagon and insulin secretion and indicate that it acts directly on the pancreatic alpha and beta cells. Glucagon secretion is approximately 20 times more sensitive to the inhibitory effects of somatostatin than is insulin secretion. Furthermore, the present results suggest that somatostatin may act by modifying cAMP-dependent systems rather than by altering cAMP levels.
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PMID:Inhibition by somatostatin of glucagon and insulin release from the perfused rat pancreas in response to arginine, isoproterenol and theophylline: evidence for a preferential effect on glucagon secretion. 111 81

If two consecutive glucose infusions are administered with 40 min of rest between, the insulin response to the second challenge is markedly potentiated. When the insulin response to the first glucose infusion was suppressed by 65% with the aid of adrenaline, potentiation of the insulin response to the second infusion was not modified. This suggests that the generation of a state of enhancement in the islet does not necessitate that glucose exerts its insulin releasing action. It is postulated that islet glucose metabolism may be involved in producing the potentiation. Pretreatment of the subjects with a glucose infusion enhanced also the insulin responses to glucagon and to tolbutamide, given intravenously 50 min later. Thus, the potentiation generated by glucose is not restricted to the insulinogenic signal induced by glucose. The eventual role that the beta-cell adenylate cyclase may play in this respect is discussed.
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PMID:Potentiation of insulin release by glucose in man. II. Role of the insulin response, and enhancement of stimuli other than glucose. 117 5

Insulin, proinsulin and glucagon extracted from lean rat pancreases were studied in radioimmunoassay, radioreceptorassay and bioassay systems. Extracted insulin behaved identically to a rat insulin used as a reference standard in radioimmunoassay. On the basis of its immunoreactivity, extracted insulin was slightly less potent (about 70%) than the rat standard insulin in competing with the binding of 125I-insulin to rat liver membranes (radioreceptorassay) and in stimulating glucose oxidation by rat fat cells (bioassay). Extracted glucagon and a pork glucagon used as a reference standard were indistinguishable in two radioimmunoassay systems for glucagon, in competing with the binding of 125I-glucagon to rat liver membranes (radioreceptorassay) and in stimulating adenylate cyclase in rat liver membranes (bioassay). Genetically obese rats (Zucker, "fatty") were compared to their lean littermates with respect to insulin, proinsulin and glucagon extracted from their pancreases. Proinsulin represented the same proportion of total immunoreactive insulin in both types of rats. In the radioimmunoassays, the radioreceptorassays and the bioassays, insulin, proinsulin and glucagon from obese rats were indistinguishable from insulin, proinsulin and glucagon from lean rats. It is concluded that the pancreatic hormones of obese ("fatty") rats possess the same immunoreactivity and biological potency as those of nonobese rats. This excludes the possibility that some alteration in the biological properties of pancreas insulin and/or glucagon of fatty rats could explain the metabolic abnormalities observed in this type of obesity.
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PMID:Glucagon and insulin from lean rats and genetically obese fatty rats: studies by radioimmunoassay, radioreceptorassay and bioassay. 120 22

Protein kinases play a pivotal role in the propagation and modulation of transmembrane signaling pathways. Two major classes of receptors, G-protein-linked and tyrosine kinase receptors not only propagate signals but also are substrates for phosphorylation in response to stimulation by agonist ligands. Insulin (operating via tyrosine kinase receptors) and catecholamines (operating by G-protein-linked receptors) are counterregulatory with respect to lipid and carbohydrate metabolism. How, on a cellular level, these two distinct classes of receptors may cross-regulate each other remains controversial. In the present work we identify a novel cross-talk between members of two distinct classes of receptors, tyrosine kinase (insulin) and G-protein-linked (beta-adrenergic) receptors. Treatment of DDT1 MF-2 hamster vas deferens smooth muscle cells with insulin promoted a marked attenuation (desensitization) of beta-adrenergic receptor-mediated activation of adenylylcyclase. Measured by immune precipitation of beta 2-adrenergic receptors from cells metabolically labeled with [32P]orthophosphate, the basal state of receptor phosphorylation was increased 2-fold by insulin. Phosphoamino acid analysis revealed that for insulin-stimulated cells, the beta 2-adrenergic receptors showed increased phosphorylation on tyrosyl and decreased phosphorylation on threonyl residues. Phosphorylation of the beta-adrenergic receptor was rapid and peaked at 30 min following stimulation of cells by insulin. beta-Adrenergic receptor phosphorylation and attenuation of catecholamine-sensitive adenylylcyclase provide a biochemical basis for the counterregulatory effects of insulin upon catecholamine action.
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PMID:Cross-talk between tyrosine kinase and G-protein-linked receptors. Phosphorylation of beta 2-adrenergic receptors in response to insulin. 128 80

Injections of parathyroid hormone (PTH) result in increased bone formation in several species. Work in our laboratory and others has shown a stimulation of bone cell proliferation and growth factor production by PTH. Our purpose was to study the effects of PTH on a human bone cell line using TE-85 human osteosarcoma cells as a model. After 24 h treatment, PTH caused an increase in cell proliferation as measured by cell counts and [3H]-thymidine incorporation. Proliferation was not inhibited by an anti-transforming growth factor beta (TGF beta) antibody which could abolish stimulation by exogenous TGF beta. PTH did not stimulate cAMP production, alkaline phosphatase activity or production of insulin-like growth factors I or II (IGF-I or IGF-II) in TE-85 cells. Although basal TE-85 proliferation was slowed by incubation with the calcium channel blocking agent verapamil, PTH still caused an increase in growth rate. We conclude that PTH directly stimulates TE-85 proliferation via a mechanism not involving increased adenylate cyclase activity or increased secretion of IGF-I, IGF-II or TGF beta and may stimulate bone formation in vivo by activating some other mitogenic signal to increase bone cell proliferation.
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PMID:PTH stimulates the proliferation of TE-85 human osteosarcoma cells by a mechanism not involving either increased cAMP or increased secretion of IGF-I, IGF-II or TGF beta. 131 2

Acquired renal cysts derive from terminally differentiated tubular epithelium in adults as a consequence of increased epithelial cell proliferation, fluid accumulation and extracellular matrix remodelling. To understand better how human epithelial cysts may be initiated and progressively expand, cells from primary cultures of normal human adult renal cortex were dispersed in polymerized type I collagen. The transparent matrix permitted repeated observation by light microscopy of cyst formation from individual renal cells. The cyst cells reacted strongly with distal nephron histochemical markers (cytokeratin antibodies AE1/AE3, epithelial membrane antigen, and Arachis hypogaea lectin) but inconsistently or not at all to markers of proximal tubules (Tetragonolobus purpureas lectin and Phaseolus vulgaris erthroagglutinin lectin). The number of spherical, fluid-filled epithelial cysts that developed in a standardized microscope field quantified cyst initiation. Cyst progression was determined from the increase in the diameter (surface area) of cysts and represents a hyperplastic event. EGF or TGF alpha, were required in serum-free defined medium to cause cysts to develop from individual epithelial cells dispersed in the matrix; insulin was required as a co-factor. The EC50 for EGF was approximately 0.1 ng/ml, and for insulin 1 microgram/ml. Early cultures of normal cortex formed cysts more efficiently when dispersed in collagen matrix than cells passaged several times before suspension in the gel. Agonists of adenylate cyclase (PGE1, AVP, VIP, PTH, forskolin, cholera toxin), methylisobutylxanthine, and 8-Br-cAMP, though incapable of causing cyst formation alone in defined medium, enhanced cyst initiation and progression in the presence of EGF and insulin. Angiotensin II, TNF alpha, beta-estradiol, and pertussis toxin had no effect in the absence or presence of EGF and insulin. Pertussis toxin inhibited cyst initiation and expansion caused by EGF and forskolin but potentiated cyst initiation and expansion caused by EGF and PGE1. Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine. Polarized monolayers of human renal cortical cells grown on permeable membranes were used to independently quantify the effects of agonists on the net secretion of solute and water from the basolateral to the apical surface of the cells. PGE1, forskolin, and 8-Br-cAMP stimulated net fluid secretion that was sustained for several days; EGF enhanced forskolin-stimulated fluid secretion. We conclude that the formation and expansion of in vitro cysts derived from solitary human cortex cells depends on the coordinated interplay between cellular proliferation and fluid secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro formation and expansion of cysts derived from human renal cortex epithelial cells. 131 21


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