Rate-dependency of calcitonin secretion in response to increased plasma Ca2+

Calcitonin (CT) is a polypeptide hormone secreted from C-cells of the thyroid gland in response to hypercalcemia. The physiological contribution of CT to calcium homeostasis has not been completely clarified. The present study therefore further characterized the sigmoidal relationship between plasma ionized calcium (P-Ca2+) and CT in normal rats, and examined the possibility of rate-dependency of CT secretion in response to changes in P-Ca2+.

Hypercalcaemia was induced by an infusion of calcium gluconate at rate of 4.5 x 10(-2) mmol h-1 rat-1 i.v. (n = 8) and hypocalcaemia was induced by an EGTA infusion at a rate of 4.5 x 10(-2) mmol h-1 rat-1 (n = 7) in one protocol: the 'slow' protocol. In another protocol an increased rate of infusion of calcium gluconate or EGTA was used to induce a more rapid change in P-Ca2+. Calcium gluconate was infused at a rate of 6.0 x 10(-2) mmol h-1 rat-1 (n = 6) and EGTA infused at a rate of 7.5 x 10(-2) mmol h-1 rat-1 (n = 7): the 'rapid' protocol.

The infusions of both the 'slow' and 'rapid' protocols resulted in linear changes in P-Ca2+, but with significantly different slopes (P < 0.01). The Ca2+/CT curves of both protocols were represented by sigmoidal curves. The 'rapid' increase of P-Ca2+ resulted in a higher maximal CT secretion (2032 +/- 215 pg mL-1) than the 'slow' increase of P-Ca2+ (1213 +/- 85 pg mL-1; P < 0.001), despite similar minimal and maximal levels being obtained in P-Ca2+ in the two protocols. Thus, a significantly greater CT response was obtained with a more rapid increment in P-Ca2+.

The relationship between P-Ca2+ and CT is represented by a sigmoidal curve, as previously shown. The CT response depended, however, not only upon the concentration of P-Ca2+ obtained but also upon the rate of increase in P-Ca2+, demonstrating rate-dependency as another significant physiological relation between Ca2+ and CT.