Interaction between adenosine generated endogenously in neocortical tissues, and homocysteine and its thiolactone

[(14)C]Adenine derivatives in normal guinea pig or rat neocortical tissues maintained by superfusion included ATP, ADP and AMP collectively forming some 98% of the acid-extracted (14)C; adenosine, inosine and hypoxanthine each at less than 0.5% and S-adenosylhomocysteine at about 0.1%. l-Homocysteine and/or its thiolactone increased only a little the S-adenosylhomocysteine. The superfusion fluid carried from the tissue per minute about 0.1% of its acid-extractable [(14)C]adenine derivatives. Electrical stimulation of the superfused tissue increased 10-fold its output of [(14)C]adenine derivatives and diminished the 5?-nucleotides in the tissue to 94% of the acid-extractable [(14)C]adenine derivatives, the remainder being adenosine, inosine and hypoxanthine with little change in S-adenosylhomocysteine. Homocysteine in the superfusion fluids now caused large increases in tissue S-adenosylhomocysteine, which became the preponderant non-nucleotide (14)C-derivative when homocysteine was 0.1 mM or greater. The total [(14)C]adenine conversion to non-nucleotide derivatives then increased and the 5?-nucleotides fell to 88% of the total. It is concluded that concentration relationships observed in the action of homocysteine make it feasible that convulsive conditions and mental changes associated with administered homocysteine and with homocystinuria are due to cerebral adenosine concentrations being diminished through formation of S-adenosylhomocysteine. Adenosine is preponderantly depressant in cerebral actions; effects of the S-adenosylhomocysteine produced may also be relevant.