Stimulation of in vitro release of calcitonin from rat and human C-cells by cimetidine.

Previous reports have suggested that the H2-receptor blocker, cimetidine, can inhibit parathyroid hormone (PTH) release. The present studies were designed in an attempt to see whether cimetidine affects secretion of calcitonin (CT) as well. Entire thyroparathyroid glands from 8-day-old baby rats or small pieces of a human medullary thyroid carcinoma were incubated at 37 C for up to 8 h in chemically defined culture medium gassed with 95% 02-5% CO2. With rat thyroparathyroids, both CT and PTH released into medium were measured using RIAs that detect that rat hormones. CT secreted from human C-cells was measured using an RIA for human CT. The results were: (A) As we had found previously, cimetidine at doses of 3 x 10(-3) M and 9 x 10(-3) M inhibited PTH release from rat thyroparathyroids by as much as 50-60% (p less than 0.05 - less than 0.001). In these same experiments, cimetidine produced increases of approximately 1- to 5-fold in the CT levels found in the medium (p less than 0.05 - less than 0.001). (B) Fragments of human medullary thyroid carcinoma incubated for 3 h in the presence of 10(-5) M cimetidine released considerably more CT than tissue incubated in control medium (48 +/- 9.3 vs 21 +/- 3.6 ng CT/microgram tissue protein, p less than 0.05). Our results show that cimetidine in vitro not only can inhibit secretion of PTH but also apparently can promote the release of CT from both rat and human C-cells. Whether this effect is mediated by H2 receptors and whether it is of any physiological significance awaits clarification.