Regulation of hormone secretion and cytosolic Ca2+ by extracellular Ca2+ in parathyroid cells and C-cells: role of voltage-sensitive Ca2+ channels.

Abstract

The two dihydropyridine enantiomers, (+)202-791 and (-)202-791, that act as voltage-sensitive Ca2+ channel agonist and antagonist, respectively, were examined for effects on cytosolic Ca2+ concentrations ([Ca2+]i) and on hormones 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 Ca2+ evoked transient followed by sustained increases in [Ca2+]i, as measured with fura-2. Increases in [Ca2+]i obtained by raised extracellular Ca2+ 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 Ca2+ channel agonist (+)202-791 stimulated whereas the antagonist (-)202-791 inhibited both transient and sustained increases in [Ca2+]i induced by extracellular Ca2+ 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 [Ca2+]i and PTH secretion in parathyroid cells. Depolarizing concentrations of extracellular K+ increased [Ca2+]i and hormone secretion in rMTC cells and both these responses were potentiated or inhibited by the Ca2+ channel agonist or antagonist, respectively. The results suggest a major role of voltage-sensitive Ca2+ influx in the regulation of cytosolic Ca2+ and hormones secretion in rMTC cells. Parathyroid cells, on the other hand, appear to lack voltage-sensitive Ca2+ influx pathways and regulate PTH secretion by some alternative mechanism.

• Authors: R Muff, E F Nemeth, S Haller-Brem, J A Fischer
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 265 Issue 1 Pg. 128-35 (Aug 15 1988) ISSN: 0003-9861 [Print] United States
• PMID: 2458067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channel Agonists
• Calcium Channel Blockers
• Ion Channels
• Nicotinic Acids
• Oxadiazoles
• Parathyroid Hormone
• PN 202-791
• Calcium

Topics

• Animals
• Calcium (metabolism, physiology)
• Calcium Channel Agonists (pharmacology)
• Calcium Channel Blockers (pharmacology)
• Cell Line
• Cytosol (drug effects, physiology)
• Extracellular Space (drug effects, physiology)
• Ion Channels (drug effects, physiology)
• Membrane Potentials (drug effects)
• Nicotinic Acids (pharmacology)
• Oxadiazoles
• Parathyroid Glands (cytology)
• Parathyroid Hormone (metabolism)
• Rats
• Thyroid Gland (cytology)