Calcium inflow in cells transfected with cloned rat and porcine calcitonin receptors

Ca ²⁺ fluxes were examined in HEK 293 cells stably expressing the rat or porcine calcitonin receptors (CTRs). Calcitonin (CT) rapidly increased cytosolic Ca ²⁺ ([Ca ²⁺ ] _i ) concentrations in these cells in a manner which was sustained in the presence of extracellular Ca ²⁺ ([Ca 2+] _e ). In cells pretreated with CT, elevation of the [Ca ²⁺ ] _e concentration resulted in a further increase in [Ca ²⁺ ] _i which was concentration-dependent with respect to both the concentration of CT and the increment of [Ca ²⁺ _e . Untransfected cells, cells transfected with vector alone, and CTR-transfected cells not treated with CT, were unresponsive to [Ca ²⁺ ] _e . The microsomal Ca ²⁺ -ATPase inhibitor thapsigargin was able to mimic both the acute [Ca ²⁺ ] _i fluxes and responsiveness to [Ca ²⁺ ] _e mediated by Cr in these cells. The CT-induced responsiveness to [Ca ²⁺ ] _e was neither mimicked by, nor affected by, activators of the cAMP or protein kinase C pathways. Treatment of cells with pertussis toxin influenced neither the primary Ca ²⁺ fluxes in response to CT or thapsigargin nor the agonist-induced [Ca ²⁺ ] _e influx. Nifedipine failed to block responses to either CT or thapsigargin. These results lead to the important conclusion that the CTR participates in receptor-activated Ca ²⁺ inflow, in which depletion of intracellular Ca ²⁺ pools leads secondarily to influx of extracellular Ca2+.