Regulation of hormone secretion and cytosolic Ca 2+ by extracellular Ca 2+ in parathyroid cells and C-cells: Role of voltage-sensitive Ca 2+ channels

Abstract

The two dihydropyridine enantiomers, (+)202-791 and (−)202-791, that act as voltage-sensitive Ca 2+ channel agonist and antagonist, respectively, were examined for effects on cytosolic Ca 2+ concentrations ([Ca 2+] i) and on hormone secretion in dispersed bovine parathyroid cells and a rat medullary thyroid carcinoma (rMTC) cell line. In both cell types, small increases in the concentration of extracellular Ca 2+ evoked transient followed by sustained increases in [Ca 2+] i, as measured with fura-2. Increases in [Ca 2+] i obtained by raised extracellular Ca 2+ were associated with a stimulation of secretion of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in rMTC cells, but an inhibition of secretion of parathyroid hormone (PTH) in parathyroid cells. The Ca 2+ channel agonist (+)202-791 stimulated whereas the antagonist (−)202-791 inhibited both transient and sustained increases in [Ca 2+] i induced by extracellular Ca 2+ in rMTC cells. Secretion of CT and CGRP was correspondingly enhanced and depressed by (+)202-791 and (−)202-791, respectively. In contrast, neither the agonist nor the antagonist affected [Ca 2+] i and PTH secretion in parathyroid cells. Depolarizing concentrations of extracellular K + increased [Ca 2+] i and hormone secretion in rMTC cells and both these responses were potentiated or inhibited by the Ca 2+ channel agonist or antagonist, respectively. The results suggest a major role of voltage-sensitive Ca 2+ influx in the regulation of cytosolic Ca 2+ and hormone secretion in rMTC cells. Parathyroid cells, on the other hand, appear to lack voltage-sensitive Ca 2+ influx pathways and regulate PTH secretion by some alternative mechanism.