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:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of a synthesized phosphodiesterase inhibitor, ZSY-27, on the secretion of pancreatic juice were investigated in dog isolated and blood-perfused pancreas, and compared with those of secretin and dopamine. Intravenous administration of ZSY-27 (0.3-1 mg/kg) elicited increases in pancreatic secretion. Intra-arterial (i.a.) administration of ZSY-27 (0.1-1 mg) also elicited increased secretion. The secretory activity of ZSY-27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 micrograms of dopamine. The concentration of bicarbonate in the pancreatic juice induced by ZSY-27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine. ZSY-27-induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced secretion was significantly potentiated by infusion of ZSY-27 (25 micrograms/min) but dopamine-induced one was not. These results suggest that ZSY-27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.
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PMID:Effects of a synthesized phosphodiesterase inhibitor, ZSY-27, on pancreatic exocrine secretion of the dog. 375 12

The effects of synthesized phosphodiesterase inhibitors, DM 9278 and HWA 285, on pancreatic exocrine secretion were investigated in isolated and blood-perfused canine pancreas. Close-arterial injections of DM 9278 (10-300 micrograms) and HWA 285 (300-3000 micrograms) caused dose-dependent increases in the flow rate of pancreatic juice and perfusion blood flow. Bicarbonate concentration in the pancreatic juice stimulated by DM 9278 (300 micrograms) or HWA 285 (3000 micrograms) was significantly higher than that in the resting pancreatic juice, although neither of the compounds affected protein concentrations in the pancreatic juice. In the secretory volume, 100 micrograms of DM 9278 corresponded roughly to 1000 micrograms of HWA 285, 0.1 units of secretin or 0.3 units of pancreozymin. These secretory and vascular effects were not modified by pretreatment with atropine or sulpiride. This study suggests that both DM 9278 and HWA 285 act directly on ductular cells of the pancreas and induce secretion of water and electrolytes.
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PMID:Effects of synthesized phosphodiesterase inhibitors, DM 9278 and HWA 285, on pancreatic exocrine secretion of the dog. 384 75

1. Guanylate cyclase activity was determined in homogenates of guinea-pig islets of Langerhans by measurement of the conversion of [alpha-(32)P]GTP into cyclic [(32)P]GMP, the reaction products being separated on columns of neutral alumina. 2. The pH optimum of the enzyme was 7.3; it showed a requirement for bivalent cations, the effectiveness of the cations tested being Mn(2+)>>Ca(2+)>Mg(2+). 3. About 70% of enzyme activity was sedimented by centrifugation at 105000g for 60min; activity was increased 2.3-fold by treatment of homogenates with 0.1% Triton X-100. 4. Guanylate cyclase activity of homogenates was increased by acetylcholine, secretin or pancreozymin, but was inhibited by adrenaline, noradrenaline or ATP. Insulin, glucagon, prostaglandins E(1) or E(2), glucose, F(-), diazoxide or glibenclamide were ineffective. 5. Determination of cyclic GMP amounts in islets by radioimmunoassay showed a basal concentration of 2.0pmol/mg of protein, which was increased by incubation of the islets in the presence of acetylcholine or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, but was unaffected by glucose. 6. Dibutyryl cyclic GMP had significant stimulatory effects on rates of insulin biosynthesis in isolated rat islets of Langerhans. 7. These results suggest a possible role for cyclic GMP in the regulation of insulin biosynthesis and secretion.
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PMID:Regulation of guanylate cyclase in guinea-pig islets of Langerhans. 415 94

1. The effects of dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) and theophylline have been tested in the stimulated and unstimulated perfused cat pancreas.2. Dibutyryl cyclic AMP (1.0 mM) elicited the secretion of water and electrolytes, but not of enzymes, from this preparation. The composition of this secretion was the same as that secreted in response to secretin. This response could be slightly potentiated by theophylline.3. Theophylline, theobromine and caffeine all markedly potentiated submaximal secretin stimulation, the relative effectiveness of these methyl xanthines being the same as that observed in the inhibition of pure phosphodiesterase prepared from beef heart.4. At high concentration, theophylline had two effects: it was capable of initiating electrolyte and water secretion alone (whilst having only a very small stimulatory effect on enzyme secretion); it also had an inhibitory effect on secretion stimulated maximally by secretin.5. Thus it was easy to mimic the action of secretin, but not pancreozymin, using dibutyryl cyclic AMP and theophylline. This suggests that the action of secretin, but not that of pancreozymin, may be mediated through cyclic AMP. Further evidence is, however, needed before these conclusions can be made with confidence.
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PMID:The actions of dibutyryl cyclic adenosine 3',5'-monophosphate and methyl xanthines on pancreatic exocrine secretion. 433 1

The adenylate cyclase system of normal mouse islets was characterized. The pH optimum of the system was 7.6. The enzyme preparation contained particulate phosphodiesterase activity. This could be removed by treatment with 0.4% (v/v) Triton X-100 or inhibited by 8mm-theophylline in the presence of 2mm-cyclic AMP (adenosine 3':5'-cyclic monophosphate). ATP at 0.32mm produced one-half maximal enzyme activity. The enzyme was stimulated in the presence of F(-) and strongly inhibited by Ca(2+). The isolated enzyme retained hormonal sensitivity and was stimulated by glucagon, pancreozymin and secretin at physiological concentrations. Glucose at 17mm, 8mm and 2mm had no direct effect on the activity of the enzyme; neither did galactose at the same concentrations. Groups of islets incubated in 17mm- or 2mm-glucose for 5 or 15min and then homogenized and assayed for adenylate cyclase activity showed no differences in adenylate cyclase activity. The results suggest that the mechanism of glucose-mediated insulin release is not via the adenylate cyclase system. Hormones, however, could mediate insulin secretion via their effects on the adenylate cyclase system.
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PMID:Insulin release from mouse islets. Effect of glucose and hormones on adenylate cyclase. 434 73

Theophylline, 3-isobutyl-1-methylxanthine (IBMX), and Ro 20-1724 each augmented the increase in cAMP and the stimulation of amylase secretion caused by vasoactive intestinal peptide (VIP) or secretin. With IBMX the dose-response curve for the stimulation of amylase secretion caused by VIP or secretin spanned a range of lower concentrations than did that obtained with Ro 20-1724, which in turn spanned a range of lower concentrations than did that obtained with theophylline. The configuration of the dose-response curve for the action of VIP on cAMP differed with each phosphodiesterase inhibitor tested. With Ro 20-1724 the dose-response curve was monophasic, whereas with the two methylxanthines the dose-response curve was biphasic. With theophylline the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. The configuration of the dose-response curve for the action of secretin on cAMP also differed with each phosphodiesterase inhibitor tested. With theophylline the dose-response curve was monophasic, whereas with Ro 20-1724 and IBMX the dose-response curve was biphasic. With Ro-20-1724 the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. These results indicate that cAMP is compartmentalized in pancreatic acinar cells and that the different compartments of cAMP are affected differently by various inhibitors of cyclic nucleotide phosphodiesterase. These findings also suggest that the different compartments of cAMP are acted on by phosphodiesterases with different sensitivities to various inhibitors.
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PMID:Effects of inhibitors of cyclic nucleotide phosphodiesterase on the actions of vasoactive intestinal peptide and secretin on pancreatic acini. 617 97

In the present study we examined the actions of various agents alone and in combination on pepsinogen secretion from dispersed gastric glands prepared from rat stomach. Potentiation of pepsinogen secretion occurred with secretin or vasoactive intestinal peptide plus carbamylcholine or cholecystokinin. The pattern of action of secretin and vasoactive intestinal peptide could be reproduced by 8-bromo-cAMP, and the pattern of action of carbamylcholine and cholecystokinin could be reproduced by the calcium ionophore A23187. A phosphodiesterase inhibitor, isobutylmethylxanthine, increased pepsinogen secretion, increased the potency but not the efficacy of the action of secretin on pepsinogen secretion, and potentiated the action of carbamylcholine on pepsinogen secretion. These results suggest that, in dispersed gastric glands from rat stomach, secretagogue-induced pepsinogen secretion can be stimulated by two different mechanisms: one mechanism is mediated by cAMP and the other is mediated by changes in cellular calcium. Secretagogues whose actions are mediated by one mechanism potentiate the actions of those secretagogues whose actions are mediated by the other mechanism.
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PMID:Potentiation of pepsinogen secretion from dispersed glands from rat stomach. 619 95

To study the regulation of pepsinogen secretion by chief cells, we have developed techniques for the isolation, enrichment, and short-term culture of chief cells from canine stomach. The fundic mucosa was enzyme dispersed and chief cells were enriched to a content of about 70% using an elutriator rotor. After 36 h in culture confluent monolayers formed that were highly enriched in chief cells. Carbachol induced a time-dependent release of pepsinogen into the medium, with about a threefold increase in pepsinogen secretion over controls found after 60 min of incubation. Carbachol stimulation of pepsinogen secretion was dose dependent, with 5 microM producing 50% of the maximal response found at a carbachol concentration of 100 microM. Atropine (100 microM) produced a rightward shift of the dose-response curve, indicating the presence of a muscarinic receptor. Dibutyryl cAMP, 8-bromo-cAMP, and forskolin also markedly stimulated pepsinogen secretion. Secretin and vasoactive intestinal peptide (VIP) stimulated pepsinogen secretion, but the response were of smaller magnitude than found with carbachol or the cAMP analogues. The phosphodiesterase inhibitor isobutylmethylxanthine also caused a small stimulation of pepsinogen secretion but did not enhance the response to secretin or VIP. These findings indicate that epithelial monolayers can spontaneously form from isolated canine chief cells and retain functional differentiation evident by a response to stimulation. Canine chief cells in culture possess muscarinic and secretin receptors and respond to cAMP.
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PMID:Regulation of pepsinogen release from canine chief cells in primary monolayer culture. 619 27

In isolated mouse pancreatic acini, vasoactive intestinal polypeptide (VIP) and secretin potentiated amylase release stimulated by cholecystokinin (CCK). VIP (1-100 nM) or secretin (100-1000 nM) alone elicited a negligible secretory response, whereas in combination with CCK, these agents induced a significantly larger response. VIP increased maximal amylase release elicited by CCK without affecting the potency with which CCK stimulated secretion. The phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine (IBMX), from 0.03-1.0 mM had effects on secretion similar to those of VIP. VIP, IBMX and 8-Br-cyclic AMP, all of which act through or mimic the action of cyclic AMP, potentiated the secretory response to maximal concentrations of CCK, carbamylcholine and the ionophore A23187, all of which act via intracellular calcium. In contrast to amylase release, stimulation of acinar glucose transport by CCK or carbamylcholine was not augmented by VIP, secretin, IBMX or 8-Br-cyclic AMP. The results indicate that for amylase release from mouse pancreas, secretagogues acting via cyclic AMP potentiate those acting via calcium. However, potentiation does not apply to all biological responses of the pancreatic acinus and each response must be studied individually.
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PMID:Interaction of cholecystokinin and vasoactive intestinal polypeptide on function of mouse pancreatic acini in vitro. 620 39

Vasoactive intestinal peptide stimulated cyclic AMP-dependent protein kinase activity in human blood mononuclear cells. The simultaneous presence of a phosphodiesterase inhibitor was required to elicit maximal activation. The apparent Ka value of half the maximal stimulation was about 60 pmol. Secretin exhibited a 170-times lower potency. Other peptides such as glucagon or insulin had no effect even at 1 microM.
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PMID:Activation of cyclic AMP-dependent protein kinase by VIP in blood mononuclear cells. 620 83


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