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Journal of Pharmacology And Experimental Therapeutics, Vol. 148, Issue 2, 202-214, 1965
Copyright © 1965 by American Society for Pharmacology and Experimental Therapeutics

EFFECTS OF CAFFEINE ON MAMMALIAN ATRIAL MUSCLE, AND ITS INTERACTION WITH ADEXOSINE AND CALCIUM

Taisija De Gubareff 1 and William Sleator Jr. 1

1 Department of Physiology, Washington University School of Medicine, St. Louis, Missouri

The present investigation shows that caffeine exerts a positive inotropic effect on guinea-pig atria at concenitrations from 0.25 mM to 1.5 mM, but with furthuer increase of caffeine contraction decreases. The striking effect of caffeine in increasing duration of transmembrane action potentials (AP) is directly proportional to caffeine concentration; AP duration reaches twice normal at about 2.5 nM caffeine.

Though differences between normal and reserpinized atria suggest that caffeine can release some endogenous catecholamines from the former, the major part of its inotropic effect is not through this process. However, the marked effect of caffeine on action potential duration, as well as that on contraction, depends strongly on the presence of calcium in the external medium. When caffeine and hugh calcium are present together, contraction strength increases instead of decreasing at low frequency, and duration of the action potential, which is shorter than normal at standard frequency, becomes much longer than normal.

It was established that caffeine antagonizes the powerful depressant effects of adenosine on contraction and action potentials of guinea-pig and human atrial musele. This result can also be explained on the assumption that caffeine acts by changing the functions of calcium within the cell, if we adopt the hypothesis that adenosine acts by prevemiting calcium from performing its normal function in the activation process.

Accepted on January 12, 1965




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