Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of heat-stable enterotoxin (ST) of Escherichia coli, cholera toxin (CT), and theophylline (a phosphodiesterase inhibitor) on ion and water transport was studied with an in vivo isolated loop system of the pig colon.2. All three agents abolished net Na absorption as a result of a decrease in the lumen to blood Na flux alone. With all three agents, net Cl absorption was reduced, but not abolished, and net HCO(3) secretion was elicited. Luminal p(CO2) was reduced with CT and theophylline from that observed in normal Ringer alone.3. Theophylline resulted in a prompt and sustained increase in both cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) levels in colonic mucosa studied in vitro. ST selectively elevated cyclic GMP, whereas CT selectively elevated cyclic AMP. These responses paralleled the time course and magnitude of response of the transepithelial electrical potential difference (psi(LB)) measured in vivo.4. Ion replacement studies in the presence or absence of theophylline showed that in the absence of Na, Cl absorption was slightly reduced and HCO(3) secretion was elicited; no further additive effects of theophylline in the absence of luminal Na were observed. In the absence of luminal Cl, net Na absorption was abolished and HCO(3) was absorbed; theophylline resulted in significant net Na and HCO(3) secretion. Theophylline also increased psi(LB) in the absence of either luminal Na or Cl.5. Results suggest that in the presence of theophylline or enterotoxin, the coupled Na-H and Cl-HCO(3) exchange processes that are normally responsible for at least half of the net NaCl absorption by this tissue are interrupted. Active HCO(3) secretion is observed and Cl absorption under these conditions can be entirely explained as a consequence of psi(LB). Thus, these studies indicate that the colon may participate in the production of diarrhoea of enterotoxigenic origin. They also suggest an important functional role of cyclic nucleotides in controlling the acidity and volume of colonic contents.
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PMID:Effect of Escherichia coli heat-stable enterotoxin, cholera toxin and theophylline on ion transport in porcine colon. 627 79

Luminal application of acid was recently shown to stimulate surface epithelial HCO3(-) transport in stomach and duodenum. Effects of some potential transmitters of this response were therefore studied in amphibian gastric fundic and proximal duodenal mucosa in vitro. Duodenal HCO3- transport, which could be titrated directly, was stimulated by dibutyryl cAMP (DBcAMP, 10(-6) M), the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-6) M), noradrenaline (10(-6) M), pancreatic glucagon (10(-8) M), and gastric inhibitory peptide (GIP, 10(-10) M). Stimulation by glucagon, but not by prostaglandin E2 (PGE2, 10(-6) M), required Cl- in the luminal solution and was prevented by furosemide (10(-3) M). This suggests that glucagon may affect HCO3(-)-Cl- exchange at the luminal membrane while transport stimulated by prostaglandins may be electrogenic. Stimulatory effects of glucagon and PGE2 were also additive. Gastric HCO3- transport, studied in tissues after inhibition of H+ secretion by histamine H2-antagonists, clearly differed from duodenum in that noradrenaline and GIP were inhibitory and DBcAMP was without effect. Stimulation of gastric HCO3- transport was observed with glucagon (10(-8) M), natural cholecystokinin (CCK, 10(-8) M), and CCK octapeptide (10(-7) M), CCK preparations had no effect in the duodenum. Although tested over a wide range of concentrations, no effect on either duodenal or gastric HCO3- transport was observed with histamine, pentagastrin, tetragastrin, urogastrone, ACTH, bombesin, motilin, secretin, serotonin, somatostatin, substance P, or vasoactive intestinal peptide.
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PMID:Gastric and duodenal HCO3- transport in vitro: effects of hormones and local transmitters. 697 77

The proximal duodenal epithelium secretes bicarbonate into an adherent mucus layer, thereby protecting the mucosa from injury by gastric acid and pepsin. While bicarbonate secretion is stimulated and inhibited by a number of agonists and antagonists, the apical anion transport pathways have not been addressed fully. The objective was to assess if apical Cl-/HCO3- exchange and Cl-:HCO3- conductance are involved in duodenal mucosal bicarbonate secretion (DMBS). In healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with either saline or 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate secretion and transepithelial potential difference (PD) were stimulated by either PGE2 or the phosphodiesterase inhibitor theophylline to increase cyclic AMP. Luminal DIDS abolished PGE2-stimulated DMBS, yet had no effect on the increase in PD and failed to significantly alter theophylline-induced DMBS and PD. Therefore, in human proximal duodenum, it appears that PGE2 and cAMP activate distinct HCO3- transport pathways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS-insensitive HCO3- conductance.
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PMID:Human proximal duodenal alkaline secretion is mediated by Cl-/HCO3- exchange and HCO3- conductance. 963 9

Cilostazol, a novel cyclic adenosine monophosphate phosphodiesterase type III inhibitor, has been developed as an antiplatelet drug with a vasodilating action on peripheral arteries. The present study was designed to test, in humans, whether cilostazol can dilate the epicardial coronary arteries and what are its hemodynamic effects. Eight patients with chest pain syndrome were subjected to serial quantitative coronary arteriography immediately before and at 30, 60 and 150min after a single oral dose of cilostazol (200mg). Luminal cross-sectional areas (mm2) at the proximal and distal sites of major coronary arteries (6 segments at each sampling time) were significantly increased at 150 min after taking the drug. The percent increases relative to the baseline values were 25+/-7 (6.8+/-0.8-->8.3+/-1.0*) and 42+/-7% (2.1+/-0.3-->3.0+/-0.4*) in the right coronary artery, 24+/-5 (5.1+/-0.7-->6.1+/-0.8*) and 28+/-10% (1.6+/-0.31-->9+/-0.3*) in the left anterior descending artery, and 14+/-6 (5.9+/-0.9-->6.6+/-0.9*) and 24+/-10% (1.3+/-0.2-->1.5+/-0.2*) in the left circumflex artery, respectively (*p<0.05 vs baseline). This action, relative to that of nitroglycerine, was between 27% and 54%. Moreover, small but sustained decreases in systolic pulmonary pressure and stroke work index were observed. Thus, cilostazol has a mild coronary vasodilating action with minimal hemodynamic effects, thereby giving it a possible role in the treatment of coronary artery disease.
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PMID:Effects of a single oral dose of cilostazol on epicardial coronary arteries and hemodynamics in humans. 1192 71