Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Bertolet, B.D. et al.

Differential antagonism of cardiac actions of adenosine by theophylline.

OBJECTIVE: To determine the relative sensitivity of cardiac A1- and A2-adenosine receptor-mediated effects to antagonism by theophylline in man. METHODS: Baseline measurements of the A-H interval (A1-adenosine receptor-mediated effect) and coronary blood flow (A2-adenosine receptor-mediated effect) were made in 10 patients with angiographically normal coronary arteries. Adenosine was then administered as a continuous intravenous infusion followed by a rapid intravenous bolus, and measurements repeated. Theophylline (5 mg/kg i.v.) was then administered, and the adenosine infusion repeated. To corroborate the results found in man, the cardiac A1- and A2-adenosine receptor-mediated effects were measured in guinea pig isolated hearts exposed to increasing concentrations of adenosine, in the absence and presence of theophylline (60 microM). RESULTS: Compared to baseline, adenosine infusion and bolus caused significant prolongation of the A-H interval (109 +/- 41 vs. 116 +/- 44 vs. 168 +/- 57 ms, respectively), and increase in coronary blood flow (46 +/- 37 vs. 86 +/- 71 vs. 172 +/- 98 ml/min, respectively). Theophylline abolished the prolongation of the A-H interval during adenosine infusion and bolus (99 +/- 36 and 107 +/- 44 ms, respectively), yet had minimal effect on the increase in coronary blood flow (63 +/- 51 and 136 +/- 121 ml/min, respectively). In guinea pig isolated hearts, theophylline was shown to significantly antagonize the A2-adenosine receptor-mediated effects only when the concentrations of adenosine were < or = 1.0 microM. CONCLUSIONS: In man, theophylline completely antagonizes the A1-adenosine receptor-mediated prolongation of the A-H interval, but has minimal effect on the A2-receptor-mediated coronary vasodilation, particularly when adenosine concentrations exceed 1.0 microM.[1]

References

Differential antagonism of cardiac actions of adenosine by theophylline. Bertolet, B.D., Belardinelli, L., Avasarala, K., Calhoun, W.B., Franco, E.A., Nichols, W.W., Kerensky, R.A., Hill, J.A. Cardiovasc. Res. (1996) [Pubmed]

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