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)

Rats were injected intravenously with cholera toxin, a potent stimulator of adenylate cyclase, and lipoprotein lipase was determined in various organs and plasma. 16 h after cholera toxin injection, lipoprotein lipase activity increased 2-6-fold in heart, diaphragm and lung and decreased to one-third in adipose tissue. An increase in lipoprotein lipase activity was seen in the plasma and in the liver, as determined by antiserum to lipoprotein lipase. The increase in heart lipoprotein lipase was preceded by a rise in cyclic AMP and continued for 24 h when cyclic AMP returned to base-line levels. Both heparin-releasable and residual lipoprotein lipase increased in the heart, but to an unequal extent. The more pronounced rise in residual activity (up to 10-fold) could have contributed to an increase in the t1/2 of heart lipoprotein lipase from 1.5 to 2.6 h. The relatively lower increase in heparin-releasable lipoprotein lipase could have been due to a loss of the enzyme from this compartment into the circulation. The effect of cholera toxin on heart and adipose tissue lipoprotien lipase was observed in fasted, fed and super-fed animals and thus appears to be independent of the nutritional state of the animal. Since cholera toxin not only mimics hormonal stimulation, but causes an exaggerated response to hormones, it made studies on some aspects of regulation of both the functional and storage forms of lipoprotein lipase in the intact organism possible.
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PMID:Modulation of lipoprotein lipase in the intact rat by cholera toxin--an irreversible agonist of cyclic AMP. 608 1

The sequence of metabolic events leading to increased calorigenesis in brown adipose tissue has been reviewed. The first step of this sequence consists in the binding of norepinephrine to adrenergic receptors of the beta1 subtype. This results in the stimulation of adenylate cyclase and activation of lipolysis via the system of protein kinases. Hormone-sensitive lipases represent the "flux-generating" step regulating mitochondrial respiration. Fatty acids released from intracellular triglyceride droplets in consequence of lipase activation play a messenger role between lipolysis and mitochondrial respiration. They stimulate respiration by serving as substrates for beta oxidation (via carnitine-dependent pathways) and (or) by simultaneously increasing mitochondrial permeability to protons (physiological "loose coupling"). The control of brown adipose tissue respiration by lipolysis represents a self-regulatory process, as excessive concentrations of fatty acids retroinhibit lipolysis. At the mitochondrial level, fatty acids appear to interact with an "uncoupling" protein (thermogenin or 32 000 relative mass protein) localized in the inner membrane that confers upon brown adipose mitochondria a unique sensitivity for fatty acid uncoupling. This explains that, contrary to other tissues, respiration is principally controlled in brown adipose tissue by substrate supply (mainly long-chain fatty acids), rather than by the phosphorylation state ratio.
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PMID:Mechanisms of stimulus-calorigenesis coupling in brown adipose tissue. 608 79

It has been suggested that lithium exerts some of its pharmacological actions by inhibition of the membrane-bound enzyme adenylate cyclase. However, the relationship between the lithium inhibition of adenylate cyclase and the corresponding physiological parameters, e.g. lipolysis, has not been investigated. In the present study it was found that lithium inhibited both the norepinephrine-induced accumulation of cAMP and release of glycerol in isolated rat fat cells, but only in the lower dose range of norepinephrine. At maximally effective concentrations of norepinephrine, where in the presence of 40 mM of lithium the formation of cAMP was reduced by approximally 40%, lipolysis remained unaffected. The basal content of cAMP and the basal release of glycerol were not inhibited by lithium. In addition to the inhibitory effect of lithium, lithium was found to stimulate the release of glycerol. This stimulatory effect of lithium may be explained by a prevention by lithium of the feedback inhibition by free fatty acids of adenylate cyclase and/or triglyceride lipase, since it could be avoided by increasing the concentration of bovine serum albumin in the incubation medium. It is concluded that lithium by inhibition of hormone-stimulated adenylate cyclase activity inhibits lipolysis only at submaximal hormone concentrations. This dissociation by lithium of cAMP accumulation and glycerol release may suggest that at least at high concentrations of norepinephrine cAMP-independent factors are involved in lipolysis.
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PMID:Dissociation by lithium of hormone-induced formation of cyclic AMP and release of glycerol in isolated rat fat cells. 624 16

The Mg2+-dependent phosphatidate phosphohydrolase activity increased in the microsomal and decreased in the soluble fraction of isolated rat fat cells incubated for short periods with the lipolytic hormones or agents, epinephrine, cyclic AMP, theophylline, and dibutyryl cyclic AMP. Adrenocorticotropin, on the other hand, increased not only the microsomal but also the soluble activity. The increases in microsomal activity ranged from 30 to 134% with epinephrine to almost 200% with dibutyryl cyclic AMP. The decreases in soluble activity were more modest. The effect of epinephrine was inhibited by the beta-adrenergic antagonist propranolol while the alpha-antagonist phentolamine enhanced it. These results strongly suggest that the fat cell phosphatidate phosphohydrolase is controlled through the beta-adrenergic receptor and the activity of adenylate cyclase. Lipolysis, as measured by fatty acid release, was stimulated in a similar pattern as the microsomal activity suggesting parallel activation of the hormone sensitive lipase and phosphatidate phosphohydrolase. It is speculated that the activation of this lipogenic enzyme by lipolytic stimuli may represent a mechanism whereby fatty acid release from adipose tissue may be modulated and intracellular fatty acid accumulation may be counteracted during accelerated lipolysis in adipose tissue.
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PMID:Control of fat cell phosphohydrolase by lipolytic agents. 626 99

The recent literature regarding the mechanisms of regulation of lipolysis with emphasis on the role of cyclic nucleotides is reviewed. The following conclusions appear warranted at present. (1) Cyclic AMP (cAMP) is a major regulator of lipolysis. However, mechanisms other than the production and catabolism of cAMP also exist. (2) Insulin can lower adipocyte cyclic AMP levels, but this effect cannot explain all aspects of the antilipolytic effect of insulin. (3) Insulin stimulates cyclic AMP phosphodiesterase and inhibits adenylate cyclase in adipocytes. In addition, there are probably other targets of insulin action. The possibilities include cAMP dependent protein kinase, phosphoprotein phosphatase, and triacylglycerol lipase. (4) Cyclic GMP is probably not directly involved in the regulation of lipolysis. (5) Cytosolic Ca2+ probably plays an important role in the regulation of lipolysis. The nature of such a role for Ca2+ and the potential role of calmodulin in the regulation of lipolysis remain to be explored.
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PMID:Cyclic nucleotides and lipolysis. 627 17

Forskolin increased cyclic AMP accumulation in isolated adipocytes and markedly potentiated the elevation of cyclic AMP due to isoproterenol. In adipocyte membranes, forskolin stimulated adenylate cyclase activity at concentrations of 0.1 microM or greater. Forskolin did not affect the EC50 for activation of adenylate cyclase but did increase the maximal effect of isoproterenol. Neither the soluble nor particulate low-Km cyclic AMP phosphodiesterase activity was affected by forskolin. Low concentrations of forskolin (0.1-1.0 microM), which significantly elevated cyclic AMP levels, did not increase lipolysis, whereas similar increases in cyclic AMP levels due to isoproterenol elevated lipolysis. Forskolin did not inhibit the activation of triacylglycerol lipase by cyclic AMP-dependent protein kinase or the subsequent hydrolysis of triacylglycerol. Higher concentrations of forskolin (10-100 microM) did increase lipolysis. Both the increased cyclic AMP production and lipolysis due to forskolin were inhibited by the antilipolytic agents insulin and N6-(phenylisopropyl)adenosine. Hypothyroidism reduced the ability of forskolin to stimulate cyclic AMP production and lipolysis. These results indicate that forskolin increases cyclic AMP production in adipocytes through an activation of adenylate cyclase. Lipolysis is activated by forskolin but at higher concentrations of total cyclic AMP than for catecholamines.
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PMID:Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes. 628 66

Phospholipase A2 (PLA2) increases adenylate cyclase (AC) activity in the rat caudate nucleus in a dose-dependent manner. After maximal stimulation by fluoride, PLA2 treatment further increases AC activity 2.4 fold. Adenylate cyclase activity is maximal after 45% hydrolysis of the phospholipids. Of the products of PLA2 treatment only lysophosphatidylcholine (LPC) produces such an increase in AC activity. In contrast to PLA2 treatment, LPC solubilizes the enzyme, decreases the Km value for ATP, and requires much larger amounts of LPC than that produced by lipase treatment. After maximal stimulation with fluoride and PLA2, removal of most of the LPC does not reduce the activity of adenylate cyclase. These findings suggest that removal of membrane lipid rather than generation of LPC is responsible for the activation of brain adenylate cyclase by phospholipase A2.
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PMID:Activation of fluoride-stimulated adenylate cyclase by phospholipase A2 in the caudate nucleus of the rat brain. 662 79

The effects of propranolol on lipid metabolism were studied in rats. Male Sprague Dawley rats at 5 weeks of age were used. Rats were given 5-10 mg/kg/day of propranolol subcutaneously or 10 mg/kg/day orally for 8 weeks. Serum non-esterified fatty acids and triglyceride were lowered in the oral treatment with propranolol but not changed in the subcutaneous one. Total serum cholesterol tended to decrease at the early weeks of treatment and increased at later weeks of treatment as compared with the control group. alpha-Lipoprotein was higher and beta-lipoprotein was lower in propranolol-treated groups than that in the control group. Serum lecithin cholesterol acyl transferase activity and high density lipoprotein were higher in propranolol-treated groups at 1st and 8th week of treatment. Total cholesterol in the liver decreased at the 8th week of treatment, but triglyceride in the liver did not change. These results suggest that propranolol inhibits the hormone sensitive lipase activity through adenyl cyclase at the early weeks of treatment, but this effect is reduced by homeostasis at the later weeks of treatment. There were some differences in serum lipids and enzyme activities between the oral and subcutaneous treatments. This would be related to the first pass effect of propranolol.
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PMID:[Effect of propranolol on lipid metabolism in rats]. 716 Jul 93

The mechanisms responsible for the diminished lipolytic response of adipocytes to catecholamines after litter removal from lactating rats and their modulation by growth hormone have been investigated. Lactation, litter removal and growth-hormone treatment did not alter the ability of noradrenaline to activate protein kinase A (A-kinase), showing that the defect in signal transduction in rats after litter removal is after A-kinase. Litter removal had no effect on hormone-sensitive lipase activity itself, but the proportion of the lipase associated with the fat droplet was decreased; growth-hormone treatment increased hormone-sensitive lipase activity and the proportion associated with the fat droplet. In addition, a number of other adaptations in the beta-adrenergic signal-transduction system occur during the lactation cycle and in response to growth hormone treatment, including changes in receptor number, adenylate cyclase activity and cyclic AMP phosphodiesterase activity, but a defect in the ability of hormone-sensitive lipase to associate with the lipid droplet appears to be the major reason for the diminished response to catecholamines on litter removal.
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PMID:Mechanisms involved in the adaptations of the adipocyte adrenergic signal-transduction system and their modulation by growth hormone during the lactation cycle in the rat. 838 54

In the previous studies we have shown that testosterone increases lipolytic responsiveness to catecholamines in rat white adipocytes, and that is associated with an up-regulation of beta-adrenergic receptor density. However, the postreceptor events involved in the testosterone induced enhancement of beta-adrenergic receptor activated lipolysis in these cells have not been adequately studied, and were therefore investigated in the present study. Male Sprague Dawley rats were divided into three groups: control, castrated, and castrated treated with testosterone. The beta-adrenergic receptor-mediated cAMP accumulation, measured with RIA after isoproterenol (a beta-adrenergic agonist) stimulation was decreased in castrated rats, and reversed by testosterone treatment, suggesting a testosterone effect at or proximal to adenylate cyclase. However, no differences between the groups were found in abundance of G alpha protein messenger RNAs (G alpha s, G alpha i-1, and G alpha i-2) as analyzed by Northern blot and a solution hybridization RNase protection assay, or in G protein mass measured with a quantitative enzyme-linked immunosorbent assay in fat cell membrane preparation. Lipolysis stimulated by N6-monobutyryl-cAMP was reduced in castrated rats and recovered by testosterone treatment, suggesting that components distal to the adenylate cyclase, i.e. protein kinase A (PKA) and/or hormone sensitive lipase (HSL) also are involved in testosterone regulation of lipolysis. In conclusion, these and previous results suggest that the testosterone-induced increase in lipolytic response to catecholamines in rat white adipocytes is mediated through several events including an increased beta-adrenergic receptor density, probably an increased adenylate cyclase activity and an increased protein kinase A/hormone sensitive lipase activity at the postreceptor level with apparent absence of effect on the expression of G-proteins.
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PMID:Postreceptor events involved in the up-regulation of beta-adrenergic receptor mediated lipolysis by testosterone in rat white adipocytes. 838 92


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