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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dose of theophylline and caffeine which do not produce aortic arch anomalies in embryonic chicks have been shown to potentiate catecholamine-induced aortic arch malformations in that experimental animal. Theophylline (2.1 X 10(-5) mole per milliliter isotonic saline solution) potentiated the effective dose of norepinephrine more than 100 times. The greatest potentiation observed with epinephrine (2.5 X) was induced by 2.6 X 10(-5) mole caffeine. This study also demonstrated that both methylxanthines specifically induce aneurysms of the ascending aorta and complete absence (or nearly complete constriction) of the right ductus arteriosus. The incidences of these types of cardiovascular malformations proved to be dose dependent with theophylline a more potent teratogen than caffeine. The mobilization of calcium and/or cyclic nucleotide phosphodiesterase inhibition by the methylxanthines are suggested as significant actions in the potentiation of catecholamine-induced aortic arch anomalies.
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PMID:The effects of methylxanthines on catecholamine-stimulated and normal chick embryos. 19 58

1. Membrane potential changes produced by adenosine and adenine nucleotides, acetylcholine, and vagus nerve stimulation were studied by intracellular recording in the sinus venosus of the frog, Rana pipiens. 2. Acetylcholine (ACh) released from the vagus nerve terminals evoked a slow hyperpolarization lasting several seconds in the cells of the sinus. Ionophoretic application of ACh from a micropipette produced a response which is similar in time course and amplitude to that evoked by vagus nerve stimulation. Bath application of ACh caused a steady hyperpolarization in quiescent preparations, or cessation of action potential generation in spontaneously active preparations. 3. Adenosine and adenine nucleotides produced hyperpolarizations when applied by addition to the bath or by ionophoresis from micropipettes. The hyperpolarization produced by ionophoresis of adenine compounds was somewhat slower than that produced by ACh. 4. Adenosine and the adenine nucleotides, 5'-AMP, 3'-AMP, 2'-AMP, and 5'-atp were virtually equipotent in their action. Adenosine was at least 1000-fold more potent than other purine and pyrimidine nucleosides or adenine. Both the ribose and adenine groups were important for agonist activity. 5. The concentrations of agonist required to produce half-maximal responses were estimated from dose--response curves as 3 x 10(-7) M for ACh and 2 x 10(-6) M for ATP. ACh is about 7 times more potent than ATP in producing a hyperpolarization. 6. Adenine compounds act directly upon the cardiac muscle fibres: bath or ionophoretically applied adenine compounds act even when transmitter release from nerve terminals is blocked with high (Mn2+) or when ACh receptors are blocked with atropine. 7. Adenine compounds act on the surface of the muscle fibre membrane. Analogues of adenosine which do not enter the cell are potent agonists of the receptor. An adenyl oligonucleotide too large to enter the cell was 2.6 times more potent per mole than adenosine in producing a hyperpolarization. Drugs such as dipyridamole and 6-(2-hydroxy 5-nitrobenzyl) thioguanosine, which are potent blockers of adenosine transport, potentiate the response of the sinus cells to adenosine. 8. Aminophylline and theophylline are competitive antagonists of adenosine action. The apparent Ki for aminophylline inhibition was 5 microM. 9. The response produced by adenine compounds is partly caused by an increase in the permeability of the membrane to K+. The maximum response to both ACh and adenine nucleotides approached the estimated level of EK or ECl. Replacing extracellular chloride with impermeant isethionate had no effect on responses to ACh or adenine nucleotides. The hyperpolarization was not produced by an activation of an ouabain-sensitive pump since 20 microM-ouabain had little effect on the response to adenosine. 10. The response to vagus nerve stimulation is completely blocked by 50 nM-atropine...
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PMID:Adenosine receptors in frog sinus venosus: slow inhibitory potentials produced by adenine compounds and acetylcholine. 31 61

1. Theophylline (10 mM) and choleragen (1 x 10(-6) g ml.-1) abolish net fluid absorption by everted sacs of rabbit ileum. Triaminopyrimidine (20 mM) and ethacrynate (0.1 mM) prevent this inhibition of net fluid movement. Replacing Ringer Cl- with isethionate prevents the theophylline-dependent decrease in fluid absorption also. 2. Ouabain (0.1 mM) abolishes net fluid movements in both control and theophylline-treated tissue. 3. With ouabain present, hypertonic NaCl (200 mM) in the mucosal solution causes net fluid secretion (serosal-mucosal flux). With theophylline added to both the mucosal and serosal solution, net fluid absorption (mucosal-serosal flux) is observed (P less than 0.001). Triaminopyrimidine (20 mM), or ethacrynate (0.1 mM), or replacement of Ringer Na+ with choline, or Ringer Cl- with isethionate all prevent the theophylline-induced reversal of osmotic flow. 4. Theophylline increases passive net flux of Na+ and Cl- from mucosal solution containing hypertonic (200 mM) NaCl+ ouabain (0.1 mM) across sheets of ileum into serosal solution containing mannitol Ringer + ouabain. The increased passive Na+ flux is blocked by triaminopyrimidine and the increased Na+ and Cl- fluxes are blocked by ethacrynate (0.1 mM). 5. The suggested route of increased NaCl leakage is via the paracellular pathway as it is inhibited by triaminopyrimidine. The increase, itself, is a consequence of the increased passive permeability of the mucosal border to Cl-, induced by theophylline or choleragen. Water is apparently electro-osmotically coupled to the paracellular Na+ leakage (100 mole water mole-1 Na+), hence increased passive leakage reverses osmotic flow. In active tissue the lateral intercellular space contains hypertonic NaCl, and hence increased leakage of NaCl across the tight-junction in theophylline or choleragen-treated tissue gives rise to net fluid secretion.
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PMID:Fluid movements across rabbit ileum coupled to passive paracellular ion movements. 46 72

When whole urinary bladders of the toad were incubated with adenosine 3',5'-monophosphate-(3)H (cyclic AMP-(3)H) > 95% of the radioactivity could be extracted from the tissue with trichloroacetic acid (TCA). The TCA-soluble radioactivity was separable by cation-exchange (Dowex-50) chromatography into residual cyclic AMP-(3)H, 5'-AMP-(3)H, adenosine diphosphate (ADP)-(3)H and inosine-(3)H. Thus, neither substantial tight binding of cyclic AMP to TCA-precipitable cell constituents nor any novel metabolite of cyclic AMP were found. On exposure of cyclic AMP-(3)H to a crude homogenate of the epithelial cells scraped from the mucosal face of the bladder, the principal metabolite was inosine-(3)H, whereas 5'-AMP-(3)H was either absent or present in undetectible amounts. However, when the homogenate included added 5'-AMP (2 x 10(-2) mole/liter), substantial quantities of 5'-AMP-(3)H were recovered. Metabolism of cyclic AMP-(3)H by homogenates of the epithelial cell scrapings from the bladder was strongly stimulated by alkalinization over the range in pH of 6-9. Theophylline inhibited metabolism of cyclic AMP only to a limit of 50%, the inhibition being limited to the OH(-)-stimulated component. These results suggest the possibility that a second pathway for metabolism of cyclic AMP may exist. If such is the case, its relationship, if any, to the ultimate biological effects of cyclic AMP within cells will be studied.
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PMID:Metabolism of adenosine 3',5'-monophosphate by epithelial cells of the toad bladder. 430 52

We studied a number of influences on theophylline binding to serum proteins using equilibrium dialysis (37 degrees), a modified Krebs-Ringer bicarbonate buffer (pH 7.4), and 8-14C-theophylline with unlabeled theophylline (30 microgram/ml) added to sera from healthy subjects. Theophylline protein binding rose by 18.6% as pH rose from 7.0 to 7.8 (percent theophylline bound = 28.2 +/- 4.3 at pH 7.0 and 46.8 +/- 4.9 at pH 7.8, n = 5). Average theophylline binding to the proteins at 37 degrees in serum samples from 10 normal adults was 39.3 +/- 3.44%, which is 89.9% lower than the average of 48.2 +/- 3.74% for the same samples at 26 degrees. Theophylline binding was 6.1% higher with 0.1 mole/l phosphate buffer, pH 7.4, than with a modified Krebs-Ringer bicarbonate buffer, pH 7.4. Of the 19 drugs and metabolites tested for competition with theophylline for binding sites on serum proteins, 10 induced decreases in binding ranging from 6.8% in the case of furosemide to 18.3% for sodium salicylate. The latter was the only drug that induced a decrease in theophylline binding at concentrations that would be achieved in the therapy of same patients (i.e., patients on long-term salicylate therapy). All the other drugs that decreased theophylline binding did so at much greater concentrations than their usual therapeutic levels. The mean +/- SD of theophylline bound in 51 fresh serum samples from healthy adults was 48.6 +/- 10.2%; the pH of these specimens varied from 7.6 to 8.7. After adjusting pH to 7.4, theophylline binding was lowered to 37.6 +/- 4.5% and intersubject variability decreased. We recommend that the pH of serum specimens be adjusted to 7.4, or to the original pH of the blood specimen if it differs significantly from 7.4 (i.e., in acidotic or alkalotic patients). The wide range of reported values for theophylline binding to serum proteins in normal and asthmatic adults at least partly results from differences in the conditions used for the separation of free from bound drug.
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PMID:Factors influencing theophylline serum protein binding. 711 64

Interaction of 1 mole of magnesium salicylate and 2 moles of theophylline in water precipitated a crystalline compound, identified as theophylline magnesium salicylate pentahydrate from analytical and supportive physicochemical data. Similarly, barium salicylate and theophylline produced theophylline barium salicylate. No precipitates were formed with calcium salicylate or strontium salicylate under the same conditions. Theophylline magnesium salicylate is not a mixture of components and differs in composition from the known theophylline calcium salicylate dihydrate. Unlike the latter compound, it is not alkaline.
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PMID:Theophylline magnesium salicylate, a new xanthine compound. 720 28

Using an in vitro incubation system, the role of the cyclic AMP-dependent protein kinase A (PKA) pathway in the regulation of the in situ activity of tyrosine hydroxylase (TH) was studied in the hypothalamuses of young and aged ovariectomized rats. Hypothalamic tissue was incubated for 60 min in medium containing 3-hydroxybenzylhydrazine dihydrochloride, a dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, and various agents that modify the activity of the PKA pathway. At the end of the incubation, the tissue was homogenized and analyzed for DOPA and TH mass. The in situ molar activity of TH was expressed as the moles of DOPA accumulating in the tissue per mole of TH per hour. Forskolin, an activator of adenylyl cyclase and the cyclic AMP agonist, (Sp)-cyclic adenosine 3',5'-monophosphothioate, significantly (P < .01) increased the in situ molar activity of TH in the hypothalamic dopaminergic (DAergic) neurons of both young and aged rats. Theophylline, a phosphodiesterase inhibitor, did not affect the TH molar activity in the hypothalamuses of aged animals but did significantly (P < .001) increase its activity in those of young rats. When vasoactive intestinal peptide was evaluated, the TH molar activity was significantly (P < .005) increased in the hypothalamuses of young rats but not in those of aged rats. It was suggested that the deficiency of DA secretion by hypothalamic DAergic neurons of aged rats may be the result of insufficient activation of PKA caused by failure of transduction of an extracellular signal to activate adenylyl cyclase and produce cyclic AMP.
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PMID:Localization of a defect in hypothalamic dopaminergic neurons of the aged brain that results in impaired PKA-dependent activation of tyrosine hydroxylase. 790 91