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)

The response of the cyclic nucleotide system (cAMP, cGMP, adenylate cyclase, guanylate cyclase, and specific phosphodiesterases) to two gastric acid secretagogues, histamine and acetylcholine, and two secretory inhibitors, prostaglandin E2 and secretin, was studied in vivo and in vitro in canine gastric fundic mucosa. Histamine and acetylcholine in vivo failed to stimulate cAMP but significantly increased cGMP; in vitro they affected neither adenylate cyclase nor guanylate cyclase. Prostaglandin E2 and secretin, however, increased cAMP in vivo and significantly stimulated adenylate cyclase in vitro. Specific phosphodiesterases were unaffected by these compounds. The changes, while not specifically localized to the acid-producing cells, are consistent with the suggestion that the control of canine gastric acid secretion may be mediated by changes in mucosal cAMP and cGMP.
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PMID:Cyclic nucleotides and the regulation of canine gastric acid secretion. 3 56

The activation energy of adenylate cyclase by p[NH]ppG in rat pancreatic plasma membranes was estimated to be 141-189 kj/mol. When a high concentration of secretin or CCK-8 (C-terminal octopeptide of cholecystokinin-pancreozimin) was added to the assay medium, the activation energy was reduced to 73 kj/mol. This hormone effect was exerted on the activation energy of the activation process of adenylate cyclase by p[NH]ppG. Indeed, when plasma membranes were preactivated with p[NH]ppG alone or with p[NH]ppG and CCK-8 and then washed, there resulted a persistent activation with low activation energy (65 and 48 kj/mol, respectively). A similar low activation energy was observed in membranes preincubated with GMP and CCK-8. The latter treatment could not induce persistent activation but facilitated the activation by p[NH]ppG, suggesting that the step of p[NP]ppG activation requiring a high activation energy in the absence of hormone had developed during preincubation with GMP and CCK-8, and had not been reversed by membrane washing. By contrast, EDTA pretreatment did not influence p[NH]ppG activation while provoking a reversible deactivation of persistently activated adenylate cyclase.
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PMID:Effect of hormone and guanyl nucleotide pretreatment on the activation energy of pancreatic adenylate cyclase. 11 1

1. Pancreatic plasma membranes containing a high adenylate cyclase activity and a low contamination by cytochrome c oxidase were isolated from the rat by sucrose density centrifugation. The preparation contained an (Mg,Ca)-ATPase of high activity with the following characteristics. 2. The ATPase activity was shown to have two apparent Km values for Mg-ATP (0.24 +/- 0.09 mM and 1.15 +/- 0.21 mM) and two apparent Km values for Ca-ATP (0.14 +/- 0.09 mM and 0.68 +/- 0.10 mM). Mg-GTP and Ca-GTP were also hydrolysed by the preparation. The phase transition temperature was 19.3 +/- 1.0 degrees C for the Mg-ATPase and 22.6 +/- 1.1 degrees C for the Ca-ATPase activities. 3. Three lines of evidence suggest that Mg-ATP and Ca-ATP were substrates for the same enzyme: Mg-dependent and Ca-dependent activities were not additive; the two activities showed the same pH optimum at 8.0; and the nonionic detergents Triton X-100, Triton X-305, Triton N-101, Lubrol P 12 A, and digitonin, produced a parallel solubilization of the two activities. 4. Enzyme activities were insensitive to potassium, sodium, ouabain, pancreozymin, carbamoyl-choline, secretin, concanavalin A, wheat germ agglutinin, and soybean lectin.
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PMID:Characterization of (Mg,Ca)-ATPase activity in rat pancreatic plasma membranes. 15 27

Four-fold increases in cyclic AMP levels were observed 5 to 10 min after rat pancreatic fragments were incubated with 10-7 M secretin or 10-6 M vasoactive intestinal polypeptide (VIP), in addition to 10 mM theophylline. From dose-response curves it appears that, on a molar basis, the potency of secretin was 20 times higher than that of VIP. It is concluded that cyclic AMP is probably the intracellular messenger of both secretin and VIP in centroacinar cells. Pancreozymin, caerulein, and the C-terminal octapeptide of pancreozymin inhibited the production of cyclic AMP observed with secretin of VIP, suggesting that the first three peptides were acting at a binding site different from the agonists, but coupled with the same adenylate cyclase. In acinar cells, secretin was able to exert slight ecbolic effects, and was also able to potentiate the effect of maximal concentrations of pancreozymin, caerulein, or the C-terminal octapeptide of pancreozymin. There was no simple correlation between amylase output and cyclic AMP levels, and copious amylase secretion was elicited even at control levels of cyclic AMP. Glucagon was neither an agonist nor an antagonist of any of the other polypeptides tested.
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PMID:In vitro interactions of gastrointestinal hormones on cyclic adenosine 3':5'-monophosphate levels and amylase output in the rat pancreas. 16 79

1. The cyclic AMP phosphodiesterase in homogenates of the submaxillary gland and pancreas was found to be associated mainly with the 300,000 times g supernatant fraction. A Lineweaver-Burk plot showed a high-affinity (Km app. = 1.6 muM) and a low-affinity (Km app. greater than 100muM) component for the cyclic AMP substrate. The enzyme was magnesium dependent, and strongly inhibited by papaverine, theophylline and caffeine. Cyclic GMP inhibited cyclic AMP phosphodiesterase, but only in concentrations greatly exceeding that of the cyclic AMP. Calcium did not alter the activity of the enzyme. The activity of the submaxillary cyclic AMP phosphodiesterase was not influenced by noradrenaline, dopamine, histamine, 5-hydroxytryptamine or gamma-amino butyric acid, and that of the pancreatic enzyme by acetylcholine, pancreozymin or secretin. 2. Adenylate cyclases from guinea-pig submaxillary gland and cat pancreas are particulate enzymes. The highest specific activity was recovered from the 1500 times g pellet. Guineo-pig submaxillary adenylate cyclase was activated by fluoride, noradrenaline, isoprenaline and adrenaline. The noradrenaline activation was blocked by the beta-adrenoceptor blocker, propranolol, but not by the alphs-adrenoceptor blocker, phentolamine. Neither acetylcholine nor carbachol had any effect on the adenylate cyclase activity. The apparent Km value for the 10- minus 4 M noradrenaline activated adenylate cyclase activity was completely aboliched by 5 mM calcium. Cat pancreatic adenylate cyclase was clearly and consistently activated by secretin, but not by pancreozymin or carbachol.
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PMID:Excitation-secretion coupling in exocrine glands. Properties of cyclic AMP phosphodiesterase and adenylate cyclase from the submaxillary gland and pancreas. 16 21

The cyclic GMP level in the ductus deferens is elevated by acetylcholine, norepinephrine, KCl, and the phosphodiesterase inhibitor SC-2964. The presence of extracellular Ca++ is required for the effects of all of these agents on cyclic GMP levels. In addition, Ca++ appears to be an important factor for the basal turnover of cyclic GMP in this tissue, but it may be less important in other tissues. These observations have led us to the following working hypothesis (Fig. 5): The interactions of some hormones or neurotransmitters with membrane receptors secondarily increase cyclic GMP formation after primarily increasing the influx of extracellular Ca++ or changing the distribution of Ca++ among intracellular pools or compartments. However, in addition to this possibility, other hormonal effects on particulate and/or soluble guanylate cyclase that do not involve Ca++ mediation must also be considered. Some agents that are known to increase cyclic GMP in tissues have been reported in preliminary communications to activate cell-free preparations of guanylate cyclase (Amer and McKINNEY, 1973; White, Ignarro, and George, 1973), but these reports have not yet been confirmed by other laboratories. Secretin has been reported to stimulate guanylate cyclase activity from several tissues (Thompson, Johnson, Lavis, and Williams, 1974), but the significance of this report is unclear since secretin has not yet been shown to increase cyclic GMP levels in any tissue. Thus, although not convincingly established, some hormones may increase particulate guanylate cyclase activity in a manner similar to that by which hormones increase adenylate cyclase activity. Alternatively, some hormones may increase soluble guanylate cyclase activity with mediating factors other than Ca++ being involved, or hormone-receptor interaction at the plasma membrane could conceivably induce a dislocation and change in effective activity of a reversibly bound, membrane-associated guanylate cyclase. Elucidating which or how many of these possibilities are operative will require thorough study and understanding of the fundamental behavior and properties of soluble and particulate guanylate cyclase activities.
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PMID:Regulation of cyclic GMP levels in the ductus deferens of the rat. 16 75

1. The effect of purified cholera toxin on secretory processes of exocrine pancreas has been studied in the isolated, saline-perfused cat pancreas and in incubated pieces of rat pancreas. 2. The toxin evoked a biphasic secretory response from the perfused cat pancreas. An initial small phase, which began within minutes of toxin application, was an artefact due to the presence of NaN3 in the cholera toxin preparation as supplied; it could be entirely reproduced by NaN3 at the concentration expected during toxin stimulation. A second, sustained phase of secretion, due to the action of the toxin proper, began within 30-60 min, increasing in magnitude for many hours and persisting in the absence of toxin. It was accompanied by a parellel rise in tissue cyclic AMP concentration, and could be potentiated by theophylline. 3. The composition of the secretion stimulated by cholera toxin resembled that evoked by secretin; e.g. it contained a high concentration of bicarbonate and only basal amounts of digestive enzymes. 4. Similarly, cholera toxin did not stimulate enzyme secretion by incubated rat pancreas, despite large rises in tissue cyclic AMP concentration. 5. Because cholera toxin has thus far been shown to have no other effect than that of stimulating adenylate cyclase, these observations support the conclusion that cyclic AMP does mediate the electrolyte secretory response of the pancreas to secretin, but offers no evidence that cyclic AMP plays a similar role in the regulation of pancreatic enzyme secretion stimulated by cholecystokinin-pancreozymin or acetylcholine.
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PMID:Effects of cholera toxin on cyclic adenosine 3',5'-monophosphate concentration and secretory processes in the exocrine pancreas. 16 3

Hepatocytes and Kupffer cells were separated from rat liver after prelabeling the Kupffer cells with colloidal iron and perfusion of the liver with digestive enzymes. The activity of several enzymes from Kupffer cells and hepatocytes was compared to validate this method of cell separation. The ratios of hepatocyte to Kupffer cell specific activities of glucose-6-phosphatase, 5'-nucleotidase, adenylate cyclase, and acid phosphatase were 20, 0.39, 0.18, and 0.078, respectively. Adenylate cyclases from hepatocytes and Kupffer cells were stimulated by fluoride ion, GTP, and catecholamines. Hepatocyte adenylate cyclase was also stimulated by glucagon, secretin, vasoactive intestinal polypeptide, and by prostaglandin E1, whereas, the Kupffer cell enzyme was completely insensitive to these hormones. The stimulation of hepatocyte adenylate cyclase by combinations of glucagon plus secretin, or glucagon plus vasoactive intestinal polypeptide, were equivalent to the sum of the individual stimulations. This suggests that the hepatocyte has specific receptors for glucagon and for vasoactive intestinal polypeptide and secretin. Prostaglandin E1 stimulation of hepatocyte adenylate cyclase was not additive to the stimulation caused by polypeptide hormones or catecholamines, nor did prostaglandin E1 decrease stimulation caused by these hormones. Although prostaglandin-sensitive adenylate cyclase was recovered with hepatocytes, 40 to 50% of the total liver prostaglandin-sensitive activity was recovered in a fraction of cell debris mixed with small cells which did not phagocytize colloidal iron.
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PMID:Stimulation of adenylate cyclase from isolated hepatocytes and Kupffer cells. 17 Dec 69

Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process.
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PMID:Hormonal regulation of pancreatic islet adenyl cyclase. 17 51

Bombesin (a tetradecapeptide), the C-terminal nonapeptide of bombesin (bombesin-NP), and litorin (a parent nonapeptide), each stimulated amylase secretion from rat pancreatic fragments. These responses were not affected by atropine. The concentrations that produced half-maximal stumulation of secretion were 0.25 nM for bombesin, 0.30 nM for bombesin-NP, and 0.07 nM for litorin, as compared to 0.12 nM for caerulein and 0.80 muM for the cholinergic agent carbamylcholine. When used at maximal concentrations, bombesin, bombesin-NP, and litorin showed no action on cyclic AMP levels in the presence of 5 mM theophylline. By contrast, caerulein and secretin increased cyclic AMP levels by 27 and 208%, respectively. Bombesin, bombesin-NP, and litorin did not activate adenylate cyclase in a purified pancreatic plasma membrane preparation, whereas caerulein and secretin increased this activity 20 and 16-times, respectively...
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PMID:In vitro action of bombesin and bombesin-like peptides on amylase secretion, calcium efflux, and adenylate cyclase activity in the rat pancreas: a comparison with other secretagogues. 18 11


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