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

Antagonism of the cardiovascular effects of adenosine by caffeine or 8-(p-sulfophenyl)theophylline.

We compared the abilities of the adenosine antagonists caffeine and 8-(p-sulfophenyl)theophylline (8-SPT) to block adenosine receptor-mediated hypotension and bradycardia in anesthetized rats. Few quantitative data exist concerning the amounts of caffeine needed to prevent the cardiovascular effects of physiologic plasma adenosine concentrations or concerning the site of action (central or peripheral) of such blockade. Thus, dose-response curves were constructed for the antagonism by caffeine or 8-SPT of the hypotension and bradycardia caused by infusing adenosine i.v. or by giving bolus i.v. injections of the adenosine analogs 2-chloroadenosine, R-phenylisopropyladenosine or N-ethylcarboxamidoadenosine. We also quantitated the suppression by caffeine or 8-SPT of the ability of adenosine to potentiate nicotine-induced hypertension and tachycardia. Caffeine (EC50 = 92 microM) and 8-SPT (EC50 = 48 microM) blocked the hypotension produced by elevating plasma adenosine levels from 1.22 to 1.74 microM. Similar drug doses were needed to inhibit the potentiation by adenosine of pressor and chronotropic responses to nicotine or to antagonize the hypotensive and negative chronotropic effects of 2-chloroadenosine, R-phenylisopropyladenosine and N-ethylcarboxamidoadenosine. As expected, neither caffeine nor 8-SPT demonstrated selectivity for A1 (predominating at the heart) vs. A2 (predominating at blood vessels) receptor subtypes. Administration of as much as 50 mg/kg i.p. of 8-SPT failed to produce detectable brain levels of the drug, demonstrating its failure to gain access to the central nervous system and indicating that the site at which the drug antagonizes the cardiovascular effects of adenosine is peripheral.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

  1. Antagonism of the cardiovascular effects of adenosine by caffeine or 8-(p-sulfophenyl)theophylline. Evoniuk, G., von Borstel, R.W., Wurtman, R.J. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
 
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