Cosecretion of calcitonin and calcitonin gene-related peptide from cultured rat medullary thyroid C cells

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Abstract
Whether C cells cosecrete calcitonin (CT) and CGRP was examined by exposing cultured rat medullary thyroid carcinoma 6–23 cells for 2 h to high medium Ca and to agents with a potential for affecting Ca‐dependent secretion. In every experiment exposure of cells to high medium Ca (2.0–2.5 mM) provoked an increased release of both peptides that was highly correlated (r = 0.73). With other test substances, also, changes in both hormones occurred in parallel. The Ca‐channel activator, BAY‐K‐8644 (10 μM) increased secretion, and this was inhibited by the Ca channel blocker, nitrendipine (10 μM). The Ca2+ ionophore, ionomycin (5 μM), increased release, and the calmodulin‐Ca channel inhibitor, phenytoin (100 μM), inhibited Ca‐induced release. The active 4β isomer of phorbol‐12,13‐didecanoate (0.1 μM), but not the inactive 4α isomer, increased secretion. The findings suggest that pathways mediating C cell secretion include plasma membrane Ca channels, intracellular [Ca2+], calmodulin, and protein kinase C. The results show that the secretory process in rat C cells involves the release of CGRP as well as CT.
Funding Information
  • Dreyfus Medical Foundation
  • NIH (AM35608)
  • USPHS Biomedical Research Support (RR-05427, RR-07205)