The endogenous urinary excretion of the purine derivatives allantoin, uric acid and xanthine plus hypoxanthine were measured in twenty-nine lambs, ten cattle (six steers, one cow and three preruminant calves) and four pigs. The sheep and mature cattle were nourished by intragastric infusion and the calves were given a milk-substitute. The pigs were fed on a purine-free diet. The excretion of total purine derivatives was substantially greater by the cattle, being 514 (SE 20.6) pmol/kg live weight (W)'" per d compared with 168 (SE 5.0) pmol/kg Wo7' per d by the sheep and 166 (SE 2.6) pmol/kg WO" per d by the pigs. Plasma from normally fed sheep, cows and pigs was incubated with either xanthine or uric acid. Sheep and pig plasma had no xanthine oxidase (EC 1.2.3.2) activity whereas plasma from cattle did. Uricase (EC 1 .7.3.3) was not present in plasma of cattle and pigs and appeared to be present in trace amounts only in sheep plasma. It is suggested that the species differences in endogenous purine derivative excretion were probably due to the different profiles of xanthine oxidase activity in tissues and particularly in the blood. This is because a high xanthine oxidase activity would reduce the chance to recycle purines, by increasing the probability of degradation to compounds which could not be salvaged.

SUMMARYThe recovery in urine of an intrajugular infusion of physiological amounts of allantoin was measured in four sheep nourished by an intragastric infusion of volatile fatty acids and casein (to eliminate rumen fermentation). The recovery was 72 % (S.E.M. 7) and the remainder was presumed to have been lost by diffusion into the gut and degradation by gut microflora. Measured in two sheep, allantoin was removed from the blood at a fractional rate of 0 30 h-1, and excreted in urine at 0 23 h-. Calculation based on creatinine excretion showed glomerular filtration rate and tubular reabsorption of allantoin to be unchanged by the intravenous infusion. Maximal tubular reabsorption at 1-28 mmol day-' was saturated by the load of endogenous allantoin alone. In a second experiment with seven normally fed sheep (28-50 kg live weight, all given I kg feed), urinary excretion and plasma concentration of allantoin were linearly related. However, the errors were such that plasma allantoin concentration would be of little value as a predictor of urinary excretion. There was a nearly twofold range in allantoin excretion (the larger animals excreting less), which implied that the supply of microbial biomass to the host animal per unit of feed ingested could be profoundly affected by feeding level.

Interactions between protein supply and the anabolic response to exogenous bovine (b) GH have been examined in two experiments using 28-35 kg lambs sustained entirely by intragastric infusion of volatile fatty acids (700 kJ/kg W 0.75 per day) into the rumen and the casein (600 mg (low protein; LP) or 1200 mg (high protein; HP)/kg W 0.75 per day) into the abomasum. Sheep received continuous i.v. infusions of bGH for 6 days in experiment 1 and for 18 days in experiment 2. Nitrogen balances were determined daily throughout both experiments and blood samples, from indwelling catheters, were assayed for GH, insulin-like growth factor-I (IGF-I), insulin and glucose. Infusion of bGH increased plasma GH concentration by five- to sixfold in all animals. There was an increase in N retention in both HP and LP animals over the first 2-3 days of GH administration. HP animals sustained higher N retentions (31%; P less than 0.05) throughout the GH administration but LP animals did not. In contrast, plasma IGF-I concentrations increased progressively over the first 72 to 96 h of GH administration in all sheep and thereafter remained significantly (P less than 0.05) elevated until termination of the GH infusion. In lambs which received both HP and LP infusion in experiment 1 the increase in IGF-I and LP infusions in experiment 1 the increase in IGF-I concentration by day 6 of GH administration was significantly (P less than 0.05) greater when they received the higher protein intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Seven measurements of the effect of clenbuterol on basal nitrogen excretion (UN,), and protein turnover were made in six female sheep. The sheep were sustained by the intraruminal infusion of energy as volatile fatty acids to provide maintenance, but given no protein (N-free) for 12 d (6 d control, 6 d clenbuterol). Clenbuterol reduced UN, by 20%, but only on day 2 of the 6 d subperiod. Protein flux (equivalent to degradation on N-free nutrition), measured on day 6 by the irreversible loss of leucine was significantly increased (12 %) by clenbuterol. Amino-N oxidation measured by N excretion was unchanged and, therefore, protein synthesis was also increased. During the 12 d N-free period, the recovery of urinary total N (Kjeldahl) as the sum of urea, ammonia, creatinine and purine derivatives, declined from 87.7 to 74.2 %. The form of this missing N was not identified. The effect of clenbuterol of increasing both degradation and synthesis is unlike that reported in the literature for animals receiving protein when, in general, synthesis is unchanged and degradation reduced. This could be due to a different effect of clenbuterol in the N-free state, or to unchanged effects on protein pools other than muscle whose relative contribution to protein metabolism is different in the N-free state.Clenbuterol : Protein turnover: Nitrogen loss : SheepWe have reported (Hovel1 et al. 1989) that the P,-adrenergic agonist clenbuterol reduced the endogenous nitrogen loss of sheep. That experiment was based on the hypothesis that the increase in N retention caused by the P,-agonists in animals given dietary protein is mediated by a decrease in body protein degradation Buttery & Dawson, 1987). We had, therefore, reasoned that the /3,-agonists might reduce the endogenous N loss of animals given energy, but no protein, and found that clenbuterol did significantly reduce endogenous N losses. Clearly, such an effect could be mediated by the drug modifying either protein synthesis, or degradation, or both, with the net effect that a reduced amount of amino acid would be lost to oxidation. The objective of the work to be reported here was to extend our observations on the effect of clenbuterol on basal N loss to measurements of protein turnover. M A T E R I A L S A N D METHODS Treatments and designSeven measurements were made of the daily endogenous N loss (UN,) during a 12 d period in six sheep (one sheep measured twice) given energy as an infusion of volatile fatty acids (VFA) into the rumen, but no protein (N-free period). The 12 d N-free period was divided into two 6 d subperiods either with or without the abomasal infusion of clenbuterol (6 10 pg/kg per d). On the last day of each 6 d subperiod, protein turnover was estimated from the irreversible loss rate of ~-[4,5-~H]leucine given by jugular infusion. For three of the * For reprints.

Endogenous allantoin derives from the breakdown of tissue nucleic acids. This study examined the effect of changes in protein supply on endogenous allantoin excretion by sheep. The animals were nourished by infusions of volatile fatty acids into the rumen and casein into the abomasum, thus avoiding ruminal microbial fermentation (i.e., no supply of exogenous nucleic acids). While a constant energy supply was maintained, the protein supply was altered in one of two ways: 1) changed from 0 to 3000 mg casein-N/kg metabolic weight (W0.75) per day in progressive steps; or 2) completely removed from an initial constant level [500 mg N/(kg W0.75.d)]. With the first alteration, endogenous allantoin excretion was not directly affected by the daily N input or N retention, but was linearly correlated with the cumulative N retention. With the second alteration, allantoin excretion increased (35-145%) on the first day after removal of the protein supply and then fell to a level equivalent to, or lower than, that before protein removal. The results suggest that the changes in endogenous allantoin excretion may reflect remodeling of the metabolic state of the animal during periods when protein supply fluctuates.