Abstract
We have studied the effects of papaverine and theophylline on the transport of adenosine by the isolated perfused rat kidney and by isolated renal luminal (L) and antiluminal (AL) membrane vesicles. In filtering isolated kidneys perfused with 0.1 mM adenosine, 1 mM papaverine inhibited adenosine removal from the perfusate by 40% and elevated the fractional excretion of adenosine from 0.4 +/- 0.1 to 0.7 +/- 0.0. Theophylline (10 mM) inhibited 0.1 mM adenosine removal in the filtering kidney by 18% and decreased the fractional excretion of adenosine to 0.2 +/- 0.1. In nonfiltering isolated kidneys perfused with 0.1 mM adenosine, 1 mM papaverine or 10 mM theophylline inhibited the rate of adenosine removal from the perfusate by 41 or 19%, respectively. Papaverine (50 or 100 microM) was a potent cis inhibitor of the initial (15 sec) rate of 1 microM [3H]adenosine influx into L and AL membrane vesicles. The influx of 1 microM [3H]adenosine was inhibited partially by 50 microM and inhibited completely by 100 microM papaverine. Papaverine at 10 microM trans stimulated the efflux of 50 microM [3H]adenosine preloaded into AL vesicles. However, theophylline (up to 100 microM) had no effect on the influx of 1 microM [3H]adenosine into L and AL vesicles. The data suggest that papaverine is a potent, direct inhibitor of adenosine transport across both L and AL membranes whereas it is likely that theophylline increases net adenosine influx across the L membrane and decreases adenosine influx across the AL membrane by indirect metabolic effects.
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