The "calcium clamp": effect of constant hypocalcemia on parathyroid hormone secretion

This report describes acute studies of parathyroid hormone (PTH) secretion and metabolism in conscious dogs, performed with a new technique, the "calcium clamp." Bolus injections and graded infusions of either calcium (Ca) or EGTA, respectively, increase or decrease plasma Ca to desired levels in 1-2 min; rapid determination of plasma Ca permits feedback control of the infusion rates to maintain the desired Ca concentration for prolonged periods. Using this technique, we have examined the effect in five dogs of a sustained (1 h) decrease in plasma Ca from 9.6 to 7.6 mg/dl on the secretion of PTH. Plasma immunoreactive PTH (IPTH) concentration in precaval blood increased within 1 min, peaked at 4-10 min (greater than 5 times control), but thereafter declined gradually to 57% of the maximum at 60 min, despite ongoing and constant hypocalcemia. Abrupt restoration of normocalcemia caused IPTH levels to decrease with an apparent half-time of 3.0 +/- 0.3 min (mean +/- SE). Thus, external feedback-regulated control of plasma Ca is possible in experimental animals. IPTH concentrations decline from the maximum during constant hypocalcemia, a new observation that suggests that PTH secretion and/or metabolism are altered progressively by the hypocalcemia.