Intestinal absorption of calcium in greyhounds: the response to intermittent and continuous administration of human synthetic parathyroid hormone fragment 1-34 (hPTH 1-34).

Long-term studies of gastrointestinal radio-calcium absorption were undertaken in adult greyhounds before and during two treatment regimes with human parathyroid hormone fragment 1-34 (hPTH 1-34). The results were correlated with plasma vitamin D metabolite levels and kinetic indices related to the balance of fluxes of calcium between plasma and the rapidly exchangeable calcium pools of bone. Compared with adult man, results obtained before treatment started showed lower indices of gastrointestinal calcium absorption and considerably higher concentrations of 24-hydroxycalcidiol in the dogs. Daily injections of hPTH 1-34 at 1.7 microgram day-1 kg-1 significantly increased indices of radiocalcium absorption and plasma calcitriol concentrations, while only causing transient calcaemic responses. The individual magnitudes of the calcaemic response correlated positively with indices of radiocalcium retention in the exchangeable pools of bone which in turn correlated positively with 'late-phase' absorption of radiocalcium from the gut. Subcutaneous infusions of hPTH 1-34 at 0.5 microgram day-1 kg-1 to the same dogs were just insufficient to cause hypercalcaemia, but increased plasma calcitriol concentrations. Indices of radiocalcium absorption were not increased. Continuous parathyroid hormone (PTH) infusion is now known to substantially down-regulate renal PTH receptor density, whereas recovery after a brief exposure to PTH occurs within 24 h. It is possible that the differences in response of the gut to the two regimes may in part be related to their differing effects on some PTH receptors.

Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs.

Nine dogs were infused at constant rates with the synthetic parathyroid peptide hPTH 1-34 (initially sc) to produce consistent hypercalcaemia. Over the final week, the infusions were iv. Radioisotopic tracers were injected iv 30 days (5 dogs) and 2 days (9 dogs) before the infusions were suddenly terminated. In 5 dogs, complete urine collections were obtained via a bladder catheter over 8 h beginning 2 h before stopping the infusions. Cessation of treatment caused small rises in the urinary Ca: creatinine ratio. Plasma calcium levels fell by a mean of 0.44 mmol/l, of which total urine calcium excretion only accounted for 55%. Immediately after the PTH infusions were stopped, consistent but transient increases were seen in the ratio of 'new' 47Ca to 'old' 45Ca label, suggesting inflow of 40Ca of high 47Ca specific activity from a fairly rapidly exchangeable bone pool. These data confirm and extend previous evidence that the immediate response of the calcium equilibrium between bone and bloodstream to rapid changes in plasma PTH concentrations in the supra-physiological range is paradoxical relative to the classical later response.