Radioisotope studies of purine metabolism during administration of guanine and allopurinol in the pig

Abstract

In pigs pre-fed guanine, some 33 per cent of [8- 14C]guanine administered orally appeared in the urine in 24 hr, principally in the form of allantoin. Little incorporation (less than 1 per cent) of radioactivity into body tissues occurred and only 5 per cent of the radioactivity could be found in the faeces. When allopurinol was added to the guanine diet the pattern of excretion of [8- 14C]-guanine changed considerably. Only 11 per cent of the radioactivity was recovered from the urine in 24 hr while 83 per cent appeared in the faeces in 3 days. Again, less than 1 per cent of the radioactivity was found in the tissues at slaughter. Intravenous administration of [8- 14C]guanine to a pig on the above mixture resulted in the rapid incorporation of approximately 50 per cent of the radioactivity into body tissues with a slow subsequent daily excretion of approximately 2 per cent of this radioactivity in faeces and urine. The finding of 13 per cent of the radioactivity in the faeces is considered evidence of purine excretion into the gut. The recovery of urinary radioactivity (34 per cent of dose) principally in xanthine, but also in hypoxanthine, showed the existence of a rapid additional route of guanine catabolism via hypoxanthine. Experimental evidence is also presented to demonstrate the existence of a reciprocal relationship between urinary [ 14C]hypoxanthine and allopurinol riboside excretion suggesting competitive inhibition of allopurinol riboside formation by hypoxanthine in vivo. In the allopurinol treated pig, orally administered [6- 14C]allopurinol was rapidly absorbed and almost totally excreted in the urine in 24 hr (90 per cent). The remainder of the radioactivity (approximately 7 per cent) was excreted in the faeces in 3 days and no radioactivity could be detected in tissue nucleic acids or in tissues to any extent (less than 0.01 per cent of the dose). The significance of these results in relation to the metabolic studies is discussed.