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The reticulorumen is now recognised to be an important site of net absorption of phosphate ions from ruminal fluid containing phosphate concentrations appropriate to those found in normal farming practice. These rates of absorption were measured in vivo from solutions placed in the washed reticulorumen, isolated in situ, in conscious, trained sheep. Reducing the ruminal sodium concentration led to reduced absorption of phosphate, suggestive that phosphate and sodium fluxes across the apical wall of the ruminal epithelial cell are linked, as they are in the kidney. Increased absorption of short chain fatty acids led to enhanced absorption of phosphate ions. Conversely, inhibition of carbonic anhydrase activity, by the addition of 1 mM acetazolamide to the ruminal fluid, led to a reduction in phosphate absorption. An increase in the acidity of the ruminal fluid also increased the absorption of phosphate, as did an increase in the ruminal Ca(2+) concentration over the range 1-4 mmol per litre. It is suggested that these effects can be accounted for by a Na(+)/H(+) antiporter coupled with a phosphate/proton symporter in the apical membrane of the ruminal epithelial cell., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

The net absorption rates of strontium ions from the ovine reticulo-rumen, isolated in situ in trained conscious animals, were measured under controlled conditions. A linear positive response was obtained from the addition of Sr2+ ions to the artificial rumen fluid. This increase in the absorption of Sr was reflected in an increase in the plasma Sr concentration. In contrast to the discrimination observed elsewhere in favour of the absorption of Ca relative to Sr, the absorption rate of Sr from the reticulo-rumen was significantly greater than that of Ca, from solutions containing the same molar concentration. A graded increase in the Sr concentration in the ruminal fluid from 1 mmol/l to 4 mmol/l led to a corresponding reduction in the absorption rate of Ca but an increase in that of phosphate. The latter result is similar to that observed when the intra-ruminal concentration of Ca2+ ions is increased. It is suggested that Ca and Sr share a common pathway for absorption from the reticulo-rumen and that this may involve coupling with the absorption of phosphate ions.

Phosphorus plays an important role in calcium and magnesium homeostasis in ruminants. In five trained sheep, each with a large rumen cannula, the isolated rumen wash technique was used to measure the magnesium and calcium absorption rates from the rumen. After one control period of measurement, the intra-ruminal phosphate concentration was increased from 2 to 10 mmol/L, and there was a significant increase in the calcium and magnesium absorption rates. The same technique was also used to demonstrate the effect of hyperphosphatemia on the absorption rates of magnesium and calcium from the forestomach. Although the absorption rates of magnesium and calcium tended to increase, the changes were not statistically significant. It is concluded that intra-ruminal phosphate concentration plays a role in the absorption of magnesium and calcium ions from the forestomach of sheep.

Under normal dietary conditions in which the phosphorus (P) intake of ruminant animals is adequate, the absorption of phosphate (Pi) ions takes place from both the fore-stomachs and the small intestine. The rate of Pi absorption from the latter appears to be at least three times greater than that from the former. When absorption of Pi ions from the reticulorumen is severely reduced, as in dietary P deficiency, the absorption of both calcium and magnesium ions from the reticulorumen becomes impaired. Thus, dietary P deficiency may play a role in the aetiology of acute grass tetany.

Five intact and four thyroparathyroidectomized (TPTX) lactating dairy cows were fitted with polyvinyl catheters implanted into the left carotid artery and the left mammary vein (for blood sampling) and into the right external jugular vein (for injections), and with a Foley catheter inserted into the urinary bladder. In these nine cows, daily morning and evening milking induced a prompt and transient rise in mammary venous blood plasma parathyroid hormone-related peptide (PTHrP)(1-34) concentrations, followed by an increase in both urinary phosphate concentration and phosphate renal clearance. Such a milking-induced phosphaturia was not observed when (tyr)34-bPTH(7-34)-NH2 (5 pmol/kg body wt) was infused during milking into the TPTX cows. These results indicate that PTHrP released systematically by the mammary gland during milking might be responsible for the observed phosphaturia.

It has been confirmed that the foetal parathyroid glands are important in development and that thyroparathyroidectomy (TXPTX) of the ovine foetus with thyroxine (T4) replacement leads to hypocalcaemia, retarded skeletal development, depressed calcification and rickets, relative to thyroidectomy plus T4 replacement. Histomorphometric and biochemical (urinary excretion of deoxypyridinoline) indices of bone resorption are also reduced. However, skeletal calcification can be restored to normal by long-term infusion of the TXPTX foetuses with phosphate and calcium sufficient to normalise the plasma Ca2+ x Pi ion product. Nevertheless, depressed resorption, reduced osteoblast numbers and delayed development persisted. The evidence suggests that the abnormally low number of resorption cavities and osteoclasts may result from the reduction in circulatory parathyroid-hormone-related protein consequent upon the removal of the foetal parathyroid glands and that this hypercalcaemic factor has a direct effect upon the process of resorption and primary trabecular remodelling of the foetal skeleton.

The duodenal and ileal absorption of 32P was studied by an in vivo method in control chicks and in chicks fed for 2 weeks a diet deficient in calcium or phosphorus. The results showed a highly significant increase in duodenal and ileal phosphate absorption in chicks fed a low calcium diet and a smaller, though also significant increase in duodenal but not ileal phosphate absorption in chicks fed a low phosphorus diet. The adaptation phenomenon concerning intestinal phosphorus absorption is presumably due in part to a compensatory increase in 1,25-dihydroxy-vitamin D3 in both deficient diets. However, much higher renal l-hydroxylase activity was found in chicks fed the low calcium diet than in chicks fed the low phosphorus diet. The results indicate that duodenal and ileal absorption of phosphate is a vitamin D mediated process, but the adaptation to a low phosphorus diet tends to be less efficient than that to a low calcium diet, especially in the ileum.

Although the inhibitory effect of glucocorticoids on the intestinal absorption of calcium is well recognized, their effect on the absorption of phosphate is less well documented. We studied the effect of the oral administration of betamethasone (BM; 25 micrograms/kg per day) on the duodenal absorption of phosphate in chicks fed normal calcium, normal phosphorus (NCaNP), normal calcium, low phosphorus (NCaLP) or low calcium, normal phosphorus (LCaNP) diets using the ligated loop technique in vivo. The daily oral administration of BM for 8 days significantly reduced the absorption of phosphate in chicks fed the NCaNP diet (21% decrease) but had less effect in chicks fed the NCaLP (14% decrease) or LCaNP (9% decrease) diets in which birds the absorption of phosphate was significantly raised (49 and 87% respectively). In one group of chicks, BM was administered for 9 days before the birds were transferred to the NCaLP or LCaNP diets. Adaptation was again unaffected by the treatment. Thirty-four per cent of the absorbed phosphate was retained in the duodenal tissue. Treatment with BM reduced the amount retained but this may have been caused by the lower weight of the duodenal segment in these chicks as BM administration markedly reduced growth rate. We have concluded that the duodenal absorption of phosphate in the chick can be inhibited by treatment with BM, although this may be secondary to the reduced rate of growth, but the increase in the absorption of phosphate caused by feeding NCaLP or LCaNP diets was unaffected by the steroid.

We have used young pigs, each prepared surgically with a Thiry-Vella loop of proximal small intestine, to study the time course of changes in the intestinal absorption of calcium, phosphate, sodium, glucose and water and on the plasma levels of 1,25-dihydroxyvitamin D after treatment of the animals with glucocorticoids. Perfusion of the intestinal loop for 6 h with a solution containing hydrocortisone or beta-methasone was without effect on the absorption of calcium or phosphate. The oral administration of betamethasone stimulated the absorption of calcium and phosphate by 15-20% for 2-3 days before the trend was reversed and absorption was progressively reduced. Chronic treatment with betamethasone inhibited only the active component of calcium and phosphate absorption. Treatment with betamethasone was associated with a sustained 25-50% increase, to a maximum by 2 days, in the absorption of sodium, glucose and water. Plasma levels of 1,25-dihydroxyvitamin D were reduced within 2 days of the start of treatment and reached a minimum (40-50% decrease) in 4-6 days. We conclude that the initial stimulation of calcium and phosphate absorption is caused by the increased absorption of water. The long-term decrease in absorption may not be caused solely by the decreased circulating levels of 1,25-dihydroxyvitamin D since absorption continued to fall for several weeks after 1,25-dihydroxyvitamin D levels had reached a minimum.

The relationship between the concentration of phosphate in plasma and parotid saliva was studied in six conscious sheep and a goat, either intact or thyroparathyroidectomized (t.x.p.t.x.), under conditions designed to minimize marked fluctuations in flow rate of saliva. A linear relationship between acutely induced changes in plasma phosphate concentration and the phosphate level in saliva has been demonstrated in both intact and t.x.p.t.x. animals. Dietary phosphorus depletion caused adaptation of salivary phosphate concentration so that less was secreted at a given concentration of plasma phosphate. Attention is drawn to the similarity between this phenomenon and that already described for the proximal renal tubule. Parathyroid hormone (PTH) was shown to reduce the salivary phosphate concentration with little or no effect on phosphataemia. The administration of 1,25-dihydroxycholecalciferol (1,25(OH)2CC) also caused a reduction in salivary phosphate concentration despite hyperphosphataemia and hypercalcaemia. It is suggested that salivary phosphate concentration can be influenced directly by the concurrent level of plasma phosphate but that this relationship can be modified by the circulating concentration of 1,25(OH)2CC and indirectly by PTH via increased production of 1,25(OH)2CC.

The effect of dietary induced hypophosphataemia on vitamin D metabolism was studied in four conscious sheep. No change in the plasma concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were found during hypophosphataemia when compared with normophosphataemia. In addition both the metabolic clearance rate and the production rate of plasma 1,25(OH)2D3 were unaltered during hypophosphataemia. This suggests that changes in circulating levels of 1,25(OH)2D3 were not necessary for the increased efficiency of intestinal phosphorus absorption seen in phosphorus-depleted hypophosphataemic sheep, and may explain why there is no increase in efficiency of intestinal calcium absorption in phosphorus depleted sheep. Increases in phosphataemia induced acutely by intravenous phosphate infusion for 3 h also had no effect on plasma 1,25(OH)2D3 concentration. It is concluded that in the sheep, unlike non-ruminant animals, chronic hypophosphataemia does not increase plasma 1,25(OH)2D3 concentrations and plays no physiological role in regulating its production or metabolism.

The effect of oral administration of betamethasone in single daily doses (25 microgram kg-1 d-1) and in single alternate-day doses (50 microgram kg-1 every other day) on the duodenal absorption of calcium, on the jejunal absorption of phosphate and on weight gain has been studied in chicks using the in vivo ligated loop technique. The daily administration of betamethasone for three weeks markedly reduced the absorption of calcium and phosphate as well as the growth rate. Alternate-day treatment lacked all these adverse effects of betamethasone and the results did not differ significantly from those in the control chicks.

The intestinal absorption of phosphate has been studied in conscious pigs, each prepared with a Thiry-Vella loop of jejunum. The feeding of diets low in either calcium or phosphorus caused a significant increase in the efficiency of absorption of phosphate from the solution used to perfuse the jejunal loop in both intact and parathyroidectomized (PTX) pigs. An intravenous infusion of parathyroid hormone (0.22 u. kg-1 h-1) into a PTX pig also enhanced the absorption of phosphate. The increase in the absorption of phosphate when the low phosphorus diet was fed was not caused by an increase in the concentration gradient of phosphate ions between the jejunal lumen and blood. It is concluded that the intestinal absorption of phosphate shows similar changes to those of calcium when diets low in calcium or phosphorus are fed and that parathyroid hormone, although capable of stimulating the absorption of phosphate, is not essential for this adaptation. These effects are probably brought about by changes in the renal production and mucosal uptake of 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D3.

The intestinal absorption of phosphate has been studied in vivo in the chick using ligated segments of duodenum and ileum. Feeding diets low in calcium (0.1%) and/or low in phosphorus (0.25%) caused an increase in the absorption of phosphate from both the duodenum and ileum. These changes are consistent with a putative increase in the renal production and mucosal uptake of 1,25-dihydroxycholecalciferol.

Six sheep were fed a diet with normal phosphorus content for 1 month after which plasma inorganic phosphorus (Pi), calcium, osteocalcin (BGP) and alkaline phosphatase concentrations were measured over a 48 h period. The same animals were then fed a low phosphorus diet for a further month prior to a second sampling period. Plasma Pi and BGP concentrations were significantly reduced after the low phosphorus diet; there was a statistically non-significant rise in plasma calcium but no change in alkaline phosphatase concentrations.