Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. 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

In dispersed acinar cells from guinea pig pancreas, cholecystokinin variants (CCK39 and CCK33) or carboxyl-terminal octapeptide of cholecystokinin (CCK-OP) caused significant increases in outflux of 45Ca, cyclic GMP, and release of amylase. In homogenates of acinar cells each peptide caused a significant increase in adenylate cyclase activity. For each function tested (1) CCK39 was equipotent with with CCK33, (2) CCK39 and CCK33 were 10 to 30 times less potent than CCK-OP, (3) the efficacies of CCK39, CCK33, and CCK-OP were the same, and (4) none of these effects were altered by concentrations of atropine sufficient to abolish the action of muscarinic cholinergic agents.
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PMID:Effect of cholecystokinin variant (CCK39) on dispersed acinar cells from guinea pig pancreas. 19 32

1 Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose-dependent fashion when added to the perfusate of the isolated saline-perfused pancreas of the cat stimulated by a supramaximal dose of secretin.2 There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration.3 Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol.4 Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 muM) reduced the secretion of amylase but did not abolish the effect.5 Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin-pancreozymin, secretin and sodium fluoride.6 Alloxanate strongly inhibited both basal and hormone-stimulated adenylate cyclase activity. Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin-stimulated activity.7 Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3',5'-monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM.8 Alloxanate (10 mM) strongly inhibited both basal and secretin-stimulated adenylate cyclase activity.9 It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems.
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PMID:The effects of alloxanate, nicotinic acid and imidazole on secretory processes and the activities of adenylate cyclase and 3',5'-AMP phosphodiesterase in cat pancreas. 20 Feb 97

In dispersed acini prepared from guinea pig pancreas, ethanol inhibited the increase in amylase secretion caused by cholecystokinin, carbachol, secretin, or vasoactive intestinal peptide. Ethanol did not alter binding of [125I] vasoactive intestinal peptide to pancreatic acinar cells or the inhibition of binding cause by secretin or vasoactive intestinal peptide. Ethanol potentiated the increase in adenylate cyclase activity and cellular adenosine 3':5'-monophosphate caused by secretin or vasoactive intestinal peptide. This potentiating action was reversible and could also be detected with straight-chain alcohols having fewer than seven carbon atoms. At sufficiently high concentrations, straight-chain alcohols having more than two carbon atoms inhibited the action of secretin or vasoactive intestinal peptide on adenylate cyclase activity, and this and this action was irreversible.
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PMID:Effects of alcohols on the actions of VIP and secretin on acinar cells from guinea pig pancreas. 22 Jan 30

Wheat germ agglutinin, but not concanavalin A or soybean lectin, inhibited the basal-and stimulated-adenylate cyclase activity which was present in a plasma membrane preparation from the rat pancreas. The inhibition by wheat germ agglutinin was rapid and sustained. It was of the non-competitive type and never exceeded 20% for Gpp (NH) p- and NaF-stimulated adenylate cyclase activity. The inhibition of secretin-stimulated activity was also non-competitive but more pronounced (57% inhibition at a wheat germ agglutinin concentration of 20 microgram/ml). For the C-terminal octapeptide of cholecystokinin-pancreozymin (OC-PZ)-stimulated cyclase, the inhibition amounted to 68% and was of a mixed type (both competitive and non-competitive). This last observation might be explained by the competitive inhibition exerted by wheat germ agglutinin on the binding of peptides of the OC-PZ family to their membrane specific receptors. The various inhibitory effects of wheat germ agglutinin were completely suppressed by incubating the membranes in the presence of ovomucoid, a N-acetyl-D-glucosamine rich glycoprotein. The possible functional implication of these results is discussed.
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PMID:Wheat germ agglutinin inhibits basal- and stimulated-adenylate cyclase activity as well as the binding of [3H] caerulein to rat pancreatic plasma membranes. 56 9

The mechanism by which intestinal secretagogues evoke fluid secretion in the small bowel and colon has been suggested to involve mucosal adenylate cyclase. Adenylate cyclase activity was assayed by conversion of [32P]ATP to [32P]cyclic AMP in a system of pure epithelial cells isolated from the small intestine of the hamster by vibration in buffer. Several gastrointestinal hormones were tested for their capacity to stimulate adenylate cyclase; vasoactive intestinal peptide and impure cholecystokinin-pancreozymin (but not the 99% pure preparation or pure cholecystokinin octapeptide) were potent stimuli, but pentagastrin, glucagon, secretin, and gastric inhibitory peptide were impotent. Two prostaglandins, PGE1 and PGE2, were potent stimuli of adenylate cyclase. Two other compounds that provoke intestinal secretion of fluid, deoxycholic acid and ricinoleic acid (castor oil), were ineffective stimuli of adenylate cyclase. These experiments do not support a clear-cut relationship between a compound's ability to stimulate adenylate cylase and its activity as an intestinal secretagogue.
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PMID:Stimulation of adenylate cyclase in homogenates of isolated intestinal epithelial cells from hamsters. Effects of gastrointestinal hormones, prostaglandins, and deoxycholic and ricinoleic acids. 56 12

1. The subcellular distribution of adenylate cyclase activity in rat pancreatic homogenates was examined after differential centrifugation. Divalent cations exerted significant effects on this distribution. In addition, the ratio of adenylate cyclase activities in the presence of the C-terminal octapeptide of cholecystokinin-pancreozymin and secretin was lower in the crude 'mitochondrial' fraction than in 'microsomal' fractions. This difference was due to the lability of cholecystokinin-pancreozymin receptors compared to secretin receptors. The Km,app of activation was affected more than the V by this lability. Such a degradation of cholecystokinin-pancreozymin receptors was markedly delayed by isolation and storage in the presence of a phospholipid mixture. 2. A simple, reasonably rapid (6 h), and easily reproducible method was developed to prepare a stable semi-purified plasma membrane fraction, characterized by a 10-fold increase in the specific activity of adenylate cyclase with respect to the whole homogenate. At variance with data obtained on crude subcellular fractions, the V of adenylate cyclase activity observed in this preparation, under maximal concentration of the C-terminal octapeptide of cholecystokinin-pancreozymin, was higher than that obtained with secretin or the vasoactive intestinal polypeptide.
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PMID:Subcellular distribution and response to gastroinetstinal hormones of adenylate cyclase in the rat pancreas. Partial purification of a stable plasma membrane preparation. 82 68

A number of regulatory peptides were investigated for their ability to elevate plasma cAMP. Pituitary adenylate cyclase activating peptide (PACAP)-27, PACAP-38, helodermin, helospectin I and II, vasoactive intestinal peptide (VIP), glucagon, parathyroid hormone (PTH), calcitonin and calcitonin gene-related peptide were among the peptides that were highly effective in raising plasma cAMP when given intravenously in equimolar doses to conscious mice. PACAP-27 and -38 were more effective than any of the other peptides. PACAP 16-38, secretin, gastrin-17, galanin, somatostatin, cholecystokinin-8s, pancreatic polypeptide, substance P, peptide YY and neuropeptide Y were inactive and also did not interfere with the PACAP-27-evoked rise in plasma cAMP levels. Repeated injections of PACAP-27 every 30 min caused a progressive reduction in the plasma cAMP response (measured 5 min after each injection). Forskolin, an activator of adenylate cyclase, dose-dependently raised the plasma concentration of cAMP and displayed a synergistic effect when given in a low dose concurrently with PTH or PACAP-38. The phosphodiesterase inhibitor rolipram dose-dependently raised the plasma concentration of cAMP. Combined treatment with PACAP-27 and a threshold dose of rolipram resulted in an exaggerated plasma cAMP response. Kidney hilus ligation suppressed the responses to PACAP-38, PTH, helodermin, helospectin, VIP, glucagon and calcitonin. Hepatectomy suppressed the response to glucagon but was without effect on the response to the other peptides. Pancreatectomy and spleenectomy reduced the response to VIP, but was without effect on the response to the other peptides. PACAP-27 stimulated cAMP efflux from the isolated rat tail vein. Hence, it cannot be excluded that blood vessels contribute to the peptide evoked plasma cAMP response in vivo.
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PMID:Neuropeptides of the vasoactive intestinal peptide/helodermin/pituitary adenylate cyclase activating peptide family elevate plasma cAMP in mice: comparison with a range of other regulatory peptides. 133 41

This study was designed to test the hypothesis that stimulation of adenylate cyclase and elevation of cAMP is involved in the signal transduction process for substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, cholecystokinin or gastrin releasing peptide in myenteric ganglia. Enzymatically dissociated ganglia from the myenteric plexus of the guinea-pig small intestine were used to study changes in levels of cAMP in response to application of the brain-gut peptides in the presence and absence of forskolin. Application of substance P and calcitonin gene-related peptide were found to increase intraganglionic cAMP in a dose-dependent fashion when a phosphodiesterase inhibitor was present. The ED50 values for substance P and calcitonin gene-related peptide were 5 microM and 0.75 microM, respectively. The presence of forskolin in the incubation medium resulted in significant upward shifts of the dose-response curves for both peptides. Neither vasoactive intestinal peptide, cholecystokinin nor gastrin releasing peptide stimulated increases in intraganglionic cAMP under the same experimental conditions used for substance P and calcitonin gene-related peptide.
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PMID:Effects of brain-gut related peptides on cAMP levels in myenteric ganglia of guinea-pig small intestine. 137 54


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