METABOLISM AND PRESYNAPTIC INHIBITORY EFFECTS OF ADENOSINE IN RAT VAS DEFERENS

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Abstract
In the rat vas deferens, adenosine caused rapid presynaptic inhibition of the twitch response stimulated at 0.2 Hz, this effect being maximal within 30 sec. The metabolism of [14C]adenosine was examined under these conditions. For 2–40juM adenosine and for incubations up to 120 sec, deamination of adenosine was quantitatively greater than incorporation into adenine ribonucleotides. Exposure of tissues to 2juM deoxycoformycin reduced deamination of 10juM [14C]adenosine by about 90%, but did not alter the presynaptic inhibitory action of adenosine. Exposure of tissues to 1juM hydroxy‐nitrobenzylthioguanosine, an adenosine uptake inhibitor, reduced the incorporation of 2–40juM [14C]‐adenosine into adenine ribonucleotides by 25–39% and potentiated the presynaptic inhibitory action of adenosine by 46–105%. Postganglionic sympathetic denervation of the tissue did not alter the metabolism of [14C]adenosine, indicating that the metabolism observed occurred almost exclusively in smooth muscle. It is concluded that the concentration of adenosine in the immediate vicinity of the presynaptic adenosine receptor is not greatly affected by deamination but is influenced by adenosine uptake. It is also possible that hydroxynitrobenzylthioguanosine may modify the affinity or intrinsic activity of the presynaptic adenosine receptor.