Production, metabolism and possible functions of adenosine in brain tissue in situ

Adenosine and H+ may act synergistically to regulate cerebral blood flow because adenosine production is enhanced under various experimental conditions associated with an imbalance between oxygen supply and oxygen need. Direct application of adenosine dilates the pial vessels, but changes in cerebral vascular resistance are not observed when adenosine is infused intraarterially. This is because adenosine does not readily cross the blood-brain barrier. The studies reported here show that in dogs the adenosine released into the interstitium is partly reincorporated into adenine nucleotides via an adenosine kinase (EC 2.7.1.20) reaction (salvage pathway) and partly degraded to inosine and hypoxanthine. However, in contrast to other tissues, the accumulation of iosine and hypoxanthine in brain tissue proceeds at a rate slower than that of adenosine because one of the degradative enzymes, namely purine-nucleoside phosphorylase (EC 2.4.2.1) is located only in the vessel wall, which is not readily permeable to adenosine. Thus, the slow access of adenosine to its degradative enzymes delays the appearance of its products, inosine and hypoxanthine.