Reversible desensitization of calcitonin secretion by repetitive stimulation with calcium

The extracellular ionized calcium concentration (Ca2+) is a main regulator of calcitonin (CT) release. Calcium-induced CT secretion differs for acute versus long-term alterations of Ca2+. Using the rat C cell line rMTC 6-23 we have investigated the effect of repetitive stimulation by Ca2+ on CT release. After a Ca-induced initial rise of CT secretion, repetitive Ca stimulation led to a decline of CT release to unstimulated levels (after about 4 h). Reversing the high Ca2+ concentration (2.0 mM) to basal (1.1 mM) for 2 h and then increasing Ca2+ again resulted in a restored stimulatory action of Ca2+ (about 100% increase above the control). In contrast, repetitive stimulation with the dihydropyridine Ca channel agonist Bay K-8644 showed an unchanged stimulatory effect, as observed for the cAMP analog 8-bromo-cAMP, too. The results indicate that the reversible desensitization of Ca-induced CT secretion might be due to a modification of the voltage-dependent Ca channels proximal to or at the site of Bay K-8644 action.