ADENOSINE A(1) RECEPTORS MEDIATE HYPOXIA-INDUCED INHIBITION OF ELECTRICALLY-EVOKED TRANSMITTER RELEASE FROM RAT STRIATAL SLICES

We have examined the role of adenosine in mediating effects of mild hy poxia on electrically evoked transmitter release. Rat striatal slices, preincubated with [H-3]dopamine and [C-13]choline, were superfused co ntinuously and stimulated electrically. Before and during the second s timulation, some slices were superfused with Krebs' solution with lowe red oxygen. This mild hypoxia caused a significant increase of the ele ctrically evoked outflow of endogenous adenosine, hypoxanthine and ino sine into the superfusion buffer, whereas electrically evoked release of [H-3]dopamine and [C-14]acetylcholine was significantly decreased. The addition of 8-cyclopentyl-1,3-dipropylxanthine, a selective adenos ine A(1) receptor antagonist, blocked the hypoxia-induced inhibitory e ffect on the evoked release of these two transmitters in a concentrati on-dependent manner. In summary, the results show that reduction of th e oxygen supply to striatal slices results in an increased release of endogenous adenosine, which, by acting on adenosine A(1) receptors, de creases the electrically evoked release of dopamine and acetylcholine. (C) 1997 Elsevier Science B.V.