Effects of adenosine transport inhibitors on adenosine- and nerve-mediated relaxations of guinea pig taenia caeci.

Dipyridamole and 6-thiobenzyl derivatives of guanosine and inosine were studied in isolated guinea pig taenia caeci with respect to their direct relaxing effects and their influence on relaxations caused by adenosine and nonadrenergic inhibitory nerve stimulation. Direct inhibitory effects were noted with all drugs at 10 microM and these were usually reversible. All inhibitors potentiated the relaxant effects of a submaximal concentration of adenosine in a concentration dependent manner and the potentiating effects persisted for at least 2-3 h after washout of inhibitors. Among the nucleoside-type inhibitors 6-[(4-nitrobenzyl-thio]-purine riboside (NBMPR) was slightly more potent and longer lasting than the others and showed less direct depressant actions. Adenosine concentration-response curves were shifted to the left by all inhibitors but relaxations caused by 2-chloroadenosine remained unaffected. Frequency response curves (0.2-5 s-1), obtained under conditions of selective stimulation of nonadrenergic inhibitory nerves, were not affected by any of the nucleoside-type inhibitors while dipyridamole caused small but significant enhancement of relaxations at low frequencies only. All inhibitors shifted concentration-response curves of adenosine, but not of 2-chloroadenosine, to the left.