Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D06103 (Theophylline)
 2,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Sodium transport across isolated frog skin, as measured by the short-circuit current, was decreased by acetylsalicylic acid, mefenamic acid, paracetamol and phenylbutazone. Indomethacin (6 X 10(-6) M) had a biphasic effect on the short-circuit current: a transient increase followed by a sustained decrease. 2. The release of prostaglandin-like material from the skin was reduced by acetylsalicylic acid and indomethacin. Paracetamol caused a significant reduction in the short-circuit current response of the skin to low doses of arachidonic acid, but the response to the highest dose tested was not significantly altered. 3. Indomethacin (6 X 10(-6) M) increased the sensitivity of the skin to applied prostaglandin E1. The other prostaglandin synthetase inhibitors did not have this effect. Indomethacin (6 X 10(-6) M) also enhanced the effect of antidiuretic hormone on the short-circuit current. 4. Indomethacin (30 X 10(-6) M) increased the short-circuit current and diminished the response to applied prostaglandin E1. 5. In sulphate Ringer, theophylline increased the short-circuit current and diminished the response to prostaglandin E1. 6. Prostaglandin E1 increased the levels of cyclic AMP in frog skin and these increases preceded the increases in short-circuit current. There was a seasonal variation in the level of cyclic AMP in the skin: the levels in winter exceeded those in summer. There was also a seasonal variation in the cyclic AMP response to prostaglandin E1: the winter response was greater than that in summer. 7. Indomethacin (6 X 10(-6) M) had a biphasic effect on cyclic AMP levels in the skin, an initial increase followed by a decrease. Indomethacin also potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 8. Theophylline increased cyclic AMP levels in the skin and potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 9. Pre-treatment of the skin with theophylline reversed the effects of cyclic AMP on the short-circuit current and open-circuit potential. 10. It is concluded that endogenous prostaglandins help to maintain sodium transport across isolated frog skin and that the effects of E-type prostaglandins on the short-circuit current are mediated by increased cyclic AMP levels. The transient increase in short-circuit current and the increased skin sensitivity caused by indomethacin (6 X 10(-6) M) are attributed to inhibition of phosphodiesterase activity. The failure of theophylline to potentiate the short-circuit current response of the skin to prostaglandin E1 is attributed to alteration of cyclic AMP action on the skin by theophylline.
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PMID:Endogenous prostaglandins, adenosine 3':5'-monophosphate and sodium transport across isolated frog skin. 18 63

The relationship between bradykinin (BK)-induced prostaglandin E2 (PGE2) and cyclic AMP syntheses in mouse fibrosarcoma cells (HSDM1C1) was investigated. Maximal BK-induced increases in cyclic AMP preceded increases in PGE2 production. PGE2 synthesis reached maximum at a much lower concentration of BK than cyclic AMP synthesis. Indomethacin completely inhibited BK-induced PGE2 production, but did not influence the cyclic AMP levels. Arachidonic acid in the medium induced PGE2 production in large quantities, but increased cyclic AMP accumulation only slightly. A high PGE2 concentration increased cyclic AMP levels only slightly. Theophylline increased basal and BK-mediated cyclic AMP levels, but did not affect PGE2 production at all. These results indicate that BK-evoked PGE2 and cyclic AMP syntheses in HSDM1C1 are not dependent upon each other.
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PMID:Bradykinin-induced cyclic AMP accumulation in mouse fibrosarcoma independent of prostaglandin E2 formation. 301 38

The action of pharmacologic agents on chymase-induced exocytosis of beta-hexosaminidase and arachidonic acid (AA) metabolism by rat serosal mast cells (RSMC) was determined and compared with their effects on anti-IgE induced activation. Indomethacin (INDO) (less than or equal to 10 microM), a cyclooxygenase inhibitor, did not affect chymase- or anti-IgE-mediated exocytosis, while completely inhibiting prostaglandin D2 (PGD2) release at 1.25 microM. Theophylline (THEO), mepacrine, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), and diethylcarbamazine (DEC), inhibitors of adenosine binding and phosphodiesterases, phospholipases, AA metabolism, and vesicular transport as well as leukotriene A4 formation, respectively, inhibited exocytosis with ID50 values of 3.4, 0.22, 3.4 and 1.9 mM for chymase and 2.4, 0.17, 2.8 and 5.2 mM for anti-IgE. These agents inhibited net PGD2 release with ID50 values of 2.1, 0.04, less than 0.05, and 1.5 mM for chymase and of 0.5, 0.1, less than 0.05, and 4 mM for anti-IgE. 5,6-Dehydroarachidonic acid (DHA) and arachidonyl hydroxylamine (AH), 5-lipoxygenase inhibitors, did not affect chymase-mediated exocytosis; anti-IgE-mediated exocytosis was not altered by AH but was suppressed by DHA (ID50 = 20 microM). Nordihydroguaiaretic acid (NDGA), an antioxidant, inhibited chymase-mediated exocytosis dose-dependently (ID50 less than or equal to 13.3 microM) while decreasing anti-IgE-mediated exocytosis by only 30% at 2.5-20 microM; net PGD2 release induced by both stimuli was inhibited dose-dependently. 2',5'-Dideoxyadenosine (DDA) and 1,6-di(0-(carbamoyl)cyclohexanone oxime)hexane (RHC 80267) and inhibitors of adenylate cyclase and of di-triglyceride lipases, respectively, had little effect on exocytosis induced by chymase but inhibited that induced by anti-IgE with ID50 values of 0.4 mM and 37 microM, respectively. With DDA the inhibition of net PGD2 release occurred with anti-IgE but not chymase, whereas RHC 80267 inhibited both chymase and anti-IgE-mediated PGD2 release. Differential inhibition of activation-secretion suggests either that chymase provides a step inhibited in IgE-mediated exocytosis by DDA, RHC 80267 and DHA, or that the activating pathway initiated by chymase is distinct.
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PMID:Pharmacological modulation of activation-secretion of rat serosal mast cells by chymase, an endogenous secretory granule protease. 393 69

The regulation of ion transport in bovine tracheal epithelium was studied in vitro. In the absence of exogenous modifiers of ion transport, average values for transepithelial electrical potential difference (psi t), short-circuit-current (Isc) and tissue resistance (Rt) were 35.4 mV (lumen negative), 5.4 muEq X h-1 X cm-2 and 187 omega X cm2 respectively; net Cl secretion (3.2 muEq X h-1 X cm-2) and net Na absorption (1.3 muEq X h-1 X cm2) accounted for 82% of the Isc. Amiloride reduced psi t and Isc, and increased Rt. The values of psi t, Rt and Isc obtained following addition of theophylline, epinephrine or prostaglandin E1 (PGE1) were not different from control values. Theophylline also did not alter Na and Cl fluxes but it increased tissue cAMP content 3-fold. Indomethacin did not affect psi t but it increased Rt and net Na absorption, and decreased Isc and net Cl secretion; it did not significantly reduce tissue cAMP. When added to indomethacin-treated tissues, epinephrine restored Isc, Rt and Na and Cl fluxes to control levels and increased tissue cAMP 3-fold. Similarly, when PGE1 was added to indomethacin-treated tissues, Isc and Rt were restored to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chloride and sodium transport across bovine tracheal epithelium: effects of secretagogues and indomethacin. 609 77

1 The histamine sensitivities of complete tracheal spiral preparations from guinea-pigs were similar to those of paired half tracheal tissues. 2 Airway muscle preparations from animals chronically treated with isoprenaline showed a significant increase in resting tone and a significant decreased responsiveness to histamine. 3 The paired half tracheal preparations exhibited no significant difference when either their isoprenaline or theophylline sensitivities were compared. 4 Paired half tracheal muscle preparations from chronically treated animals (0.4 mumol, 4.0 mumol, and 40.0 mumol isoprenaline, 3 times daily for 21 days, s.c.) showed a significantly reduced sensitivity to isoprenaline when compared to appropriate controls. 5 Theophylline concentration-effect curves for the paired half tracheal preparations from chronically treated guinea-pigs (4.0 mumol and 40.0 mumol isoprenaline) were significantly reduced compared with appropriate controls. 5 Indomethacin treatment reversed the isoprenaline desensitization induced by chronic treatment (0.4 mumol isoprenaline) but was ineffective in animals that received the higher doses of isoprenaline in vivo.
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PMID:Tolerance of guinea-pig airway muscle preparations to relaxant agonists induced by chronic exposure to isoprenaline in vivo. 626 81

The action of X-rays (50 kV, filtered by 0.3 mm Al) on helical strip of frog aorta (rana esculenta) has been investigated. The isolated preparations have a stable basal tone and are radio-sensitive to X-rays which induce reversible, dose-dependent, contractile responses. After repeated irradiation tachyphylaxis appears. The threshold doses are about 250 Rat 3 to 6 kR/min, antiadrenergic (phentolamine, propranolol), anticholinergic (atropin), antihistaminic (Neo-Bridal) and serotoninergic (Deseril) drugs have no visible influence on the X-ray induced reaction, i.e. these action mechanisms of the irradiation-induced contraction do not seem probable. Theophylline and cAMP inhibit the X-ray contraction probably non-specifically. Indometacin also inhibits the X-ray contraction: this suggests participation of prostaglandin-mechanism on the contraction of frog aorta after irradiation.
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PMID:Contractile reaction of isolated frog aorta after X-irradiation. 631 Aug 30

Amounts of prostaglandin E and prostaglandin F have been measured by radioimmunoassay in extracts of renal cortical carcinoma and benign and malignant breast tumours after solvent extraction and column chromatography. 2. Substantial amounts of prostaglandin E were found in extracts of benign and malignant breast tumours and in renal tumours. Much lower amounts of prostaglandin F were present in all tumour types. 3. Co-cultivation of tumour explants with mouse calvaria led to significant bone resorption in 10 of 13 renal carcinomas, three of eight malignant breast tumours, and two of nine benign breast tumours. Tumours associated with bone resorption had higher concentrations of prostaglandin E in culture media at the end of incubation than did non-resorbers. 4. Indomethacin (14 mumol/1) greatly reduced bone resorption in the presence of the tumour, but this was not always complete, particularly with breast tumours. Indomethacin had no effect on prostaglandin-induced bone resorption. Theophylline (2.2 mmol/1) significantly increased prostaglandin E production and resorption by an effect on the tumour. 5. It is concluded that prostaglandins may be important in mediating the effects of renal cortical carcinoma and possibly breast cancer on bone destruction. A non-prostaglandin mechanism may also contribute to bone destruction by breast carcinoma.
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PMID:Prostaglandins as mediators of bone resorption in renal and breast tumours. 736 61

Purinoceptor-mediated responses were characterized in the ileum of Suncus murinus. Adenosine as well as adenosine 5'-triphosphate (ATP) contracted the ileum in a concentration-dependent manner. Contractile responses to transmural electrical stimulation were attenuated by adenosine only at high concentrations. Theophylline competitively blocked the adenosine-induced contraction. Atropine also inhibited the adenosine-induced contraction but in a non-competitive manner. The ATP-induced contraction was not affected by theophylline, atropine or alpha, beta-methylene ATP. Indomethacin shifted the concentration-response curves for adenosine and ATP to the right. These results suggest that adenosine elicited contractions via direct stimulation of postsynaptic P1-purinoceptors and postsynaptic potentiation of the acetylcholine response. Suncus ileum will be a unique model for the analyses of purinoceptor-mediated responses.
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PMID:Adenosine induces contractions in suncus ileum. 812 Oct 76