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

Injection of 3':5'-cyclic AMP (cAMP) into larvae of the fly Sarcophaga bullata 3-4 hr before the beginning of puparium formation (red-spiracle stage) greatly accelerates the onset of tanning without affecting initiation of puparium formation (anterior retraction). Accelerated tanning resembles real tanning in two important respects: the solubility of cuticular proteins becomes reduced and [U-14C]tyrosine is incorporated into the cuticle. Of a number of cAMP analogues tested, 3':5'- cyclic GMP, 2':3'-cyclic AMP, and 5'-AMP were inactive, dibutyryl-3':5'-cAMP had only slight activity, and cyclic IMP and deoxy-3':5'-cAMP showed some activity. Theophylline enhanced the effect of small doses of cAMP or of blood, diluted 1:8, active in the puparium tanning factor. Injection of dopa, dopamine, acetyldopamine, or epinephrine, but not of tyrosine, had an accelerating effect similar to that of cAMP. The tanning-inhibiting effect of DL-alpha-methyl-alpha-hydrazino-beta-(3,4-dihydroxyphenyl)propionic acid monohydrate is reversed by dopamine or epinephrine, but not by tyrosine, dopa, or cAMP. Evidence is presented to indicate that the responses to cAMP are not artifacts but reflect actual biochemical events during tanning.
 ...
PMID:3':5'-cyclic AMP and hormonal control of puparium formation in the fleshfly Sarcophaga bullata. 19 50

Part of the soluble cyclic nucleotide phosphodiesterase activity of crude human lung tissue can be attributed to a thermosensitive (37 degrees) enzyme with a high apparent affinity for both adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP). The enzyme can be partially purified by DEAE-Sephadex chromatography. In the presence of 0.1 mM EDTA or ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (EGTA), it is eluted from the column immediately before a cyclic GMP-specific phosphodiesterase, but in the presence of 0.2 mM Ca2+, the elution follows that of the cyclic GMP-specific enzyme. The two forms of the nonspecific phosphodiesterase activity are referred to as DEAD-Sephadex Fractions Ia and Ic, respectively. Their apparent molecular weights, recorded at gel filtration, vary with different preparations from 230,000 to 150,000. Occasionally, corresponding recordings for main peaks of activity also cluster round the values 120,000, 105,000, and 78,000. The enzymatic properties of Fractions Ia and Ic closely resemble each other. The enzyme activity is blocked by EDTA, partially inhibited in the presence of 1,10-phenanthroline, but only slightly affected by EGTA. The inhibitory effect of EDTA can be overcome by Mg2+ and Mn2+ and that of 1,10-phenanthroline, in part, by Zn2+; this cation in itself is inhibitory at millimolar concentrations. With submicromolar substrate concentrations, the activity of either fraction obeys linear kinetics displaying an apparent Km of approximately 0.4 micron for both substrates. Reciprocal inhibition experiments suggest that hydrolysis of both cyclic AMP and cyclic GMP is performed by the same active site. Examination of the activity using extended substrate concentration ranges indicates nonlinear kinetics; Hill plots of such data also show nonlinear curvature. The activity is inhibited by micromolar concentrations of inosine 3':5'-monophosphate (cyclic IMP), 3-isobutyl-1-methylxanthine, papervine, and some antiallergic agents. Theophylline and disodium cromoglycate are less potent inhibitors. Inhibition of activity by Lubrol PX follows a biphasic dose response curve. The activity of Fraction Ia can be enhanced 2- to 3-fold by a Ca2+-dependent activator prepared from lung tissue, whose action is counteracted by chlorpromazine, and by lysophosphatidylcholine. It is initially enhanced but subsequently decreased at exposure to trypsin. Fraction Ic is less prone to activation by these agents. The results indicate that the present activity represents an enzyme form that differs from three previously described phosphodiesterases of human lung tissue. It is apparently related to, but also shows distinct differences from the Ca2+-dependent enzyme(s) of brain and heart tissue.
 ...
PMID:Cyclic nucleotide phosphodiesterase. Partial purification and characterization of a high affinity enzyme activity from human lung tissue. 20 35

The isolated kidney of the recipient rat was perfused at a fixed flow rate with blood from a donor by a cross-circulation technique. The renal vasculature responded to the release of arterial occlusion with vasoconstriction, the magnitude of which was increased with increase in the duration of occlusion. ATP, ADP, AMP, adenosine, noradrenaline and 5-HT injected into the renal artery induced a prominent vasoconstriction; IMP and inosine had only a weak vasoconstrictor effect even in large doses. Theophylline reduced the vasoconstriction in response to arterial occlusion and to ATP and adenosine but did not affect that produced by noradrenaline or 5-HT. This suggests that adenine compounds, particularly adenosine, may play a role in the genesis of reactive vasoconstriction after arterial occlusion in the isolated rat kidney.
 ...
PMID:A possible purinergic mechanism for reactive ischemia in isolated, cross-circulated rat kidney. 53 46

The action of 21 purine compounds on the twitch response of the electrically stimulated guinea pig isolated ileum has been investigated. Adenosine and related compounds produced a dose-dependent depression of the response. Adenosine was the most potent and 2'-deoxyadenosine had one hundredth the potency of adenosine. Adenine, hypoxanthine, inosine, IMP, ITP, xanthine, xanthosine, XMP, XTP, guanine, GMP and GTP were ineffective at concentrations less than 1 mM. Adenosine (30 microgram) reduced the electrically induced ACh output from the ileal strips. The dose--depression curve for adenosine (0.1--30 microgram) was shifted to the right in the presence of xanthine derivatives and of these, theophylline was the most potent inhibitor of adenosine. On the other hand, dipyridamole (0.1--1 microgram) and hexobendine (0.1--1 microgram) shifted the curve to the left. They markedly inhibited 3H-adenosine uptake into the ileum. Theophylline (0.1 mM), dipyridamole (0.3 microgram) and hexobendine (0.3 microgram) did not affect tetrodotoxin-, adrenaline-, strychnine- and morphine-induced inhibition of the twitch response. The present investigations have revealed that adenosine and related compounds reduce ACh release from the intramural cholinergic nerves in the guinea pig ileum possibly in a specific manner (or through a specific receptor site) different from that of other inhibitors such as morphine.
 ...
PMID:Effects of purine compounds on cholinergic nerves. Specificity of adenosine and related compounds on acetylcholine release in electircally stimulated guinea pig ileum. 63 57

1. In adult cats, postganglionic nerve fibres on the surface of the bladder were isolated and multiunit activity of these fibres was recorded. In these cats, the urinary bladder was cannulated and intravesical pressure was also recorded. 2. ATP, APPCP, ADP, AMP and adenosine depress transmission in vesical parasympathetic ganglia equipotently; however, 2-chloroadenosine was 10-fold more potent than ATP. 3. 2-chloroadenosine, ATP, ADP, AMP, adenosine and APPCP inhibit neurally evoked bladder contractions in the same order or potency with which they depress pelvic ganglionic transmission; however, adenine, inosine, IMP and ITP were ineffective. 4. 3',5'-cyclic AMP and dibutyryl cAMP produced little or no effect on bladder activity. 5. ATP and APPCP produced a transient rise in intravesical pressure at doses 2 to 50 times the dose needed for inhibition, presumably through ATP (P2) receptors. APPCP was 10 to 20 times more potent in exciting the bladder than ATP. 6. Theophylline and caffeine effectively antagonized purinergic effects mediated through adenosine (P1) receptors on both pelvic ganglia and bladder smooth muscle. 7. ATP inhibition of TMA-evoked bladder contractions and postganglionic nerve firing suggests that purinergic inhibition occurs, at least in part, at a postsynaptic site in the ganglia.
 ...
PMID:The effects of purine nucleotides on transmission in vesical parasympathetic ganglia of the cat. 254 17

Human seminal plasma contains two enzyme activities both capable of dephosphorylating all nucleoside 5-monophosphates with different efficiency and specificity. Broad-spectrum soluble 5'-nucleotidase is the object of this paper which deals with the definition of the response of this enzyme to effectors, some physiological and others not naturally occurring. The enzyme did not show any product regulation as all the nucleosides tested caused a moderate effect on the hydrolysis of the substrates. Theophylline and other xanthine derivatives had no effect on enzyme activity, whereas glycerate 2,3-bisphosphate, like other soluble 5'-nucleotidases, caused a stimulation of the enzyme, especially toward CMP and UMP. 5-Deoxy-5-isobutylthiadenosine resulted in no inhibition of the hydrolysis of AMP and IMP. The enzyme was affected neither by monovanadate nor by decavanadate, whereas it was strongly inhibited by Ap5 A. Variations in adenylate energy charge did not cause any alteration of the enzyme activity toward AMP and only a slight decrease of the hydrolysis of IMP. These regulatory properties, distinct from those of other soluble 5'-nucleotidases, show that this form, newly isolated from human seminal plasma, is subject to an almost unique, tissue-specific regulation.
 ...
PMID:Human seminal plasma soluble 5'-nucleotidase: regulatory aspects of the dephosphorylation of nucleoside 5'-monophosphates. 923 3

We report an 81-year-old woman who suffered from theophylline-associated seizures followed by partial seizures due to vitamin B6 deficiency. She developed complex partial seizures. She had been treated with theophylline for two months because of chronic bronchitis. Brain diffusion-weighted magnetic resonance imaging (MRI) showed high intensity lesions in unilateral cerebral cortex and thalamus. Electroencephalogram presented periodic lateralized epileptiform discharges (PLEDs), and single photon emission computed tomography (SPECT) using 123I-IMP revealed increased blood flow in the same side of the cerebrum. We diagnosed as theophylline-associated seizures though blood theophylline concentration disclosed its therapeutic dose, and her symptom improved after theophylline was discontinued. She developed partial seizures again, after she suffered from diarrhea for two days. Laboratory examination showed that serum vitamin B6 was under the limitation of measurement, and intravenous supplementation of vitamin B6 stopped her seizures immediately. Theophylline may induce seizures independent of its blood concentration, and vitamin B6 deficiency may exist in the case of theophylline-associated seizures.
 ...
PMID:[Case of an 81-year-old woman with theophylline-associated seizures followed by partial seizures due to vitamin B6 deficiency]. 1832 6