Interaction between extracellular calcium and endothelin-1 influences parathyroid hormone secretion from bovine parathyroid cells through the increase in intracellular calcium.
Endothelin-1 (ET-1) secretion from bovine parathyroid cells (bPTCs) responds to the changes in extracellular calcium concentrations ([Ca2+]c) and ET-1 inhibits parathyroid hormone (PTH) secretion. However, the effect from the interaction between [Ca2+]e and ET-1 on PTH secretion is unknown. To clarify these issues, a bPTC suspension was used to study the regulation of ET-1 secretion by subtle changes in [Ca2+]e and PTH secretion by the interaction between [Ca2+]e and ET-1. We added [Ca2+]e at varying concentrations, 0.5-2.0 mM, to the bPTC medium to define the relationship between [Ca2+]e and ET-1 secretion and found that the ET-1 secretion was inversely regulated by [Ca2+]e with a low [Ca2+]e stimulating, and a high [Ca2+]e inhibiting ET-1 secretion. It is even suppressed to an undetectable level at a [Ca2+]e of > 1.5 mM. Further, we worked to determine how the interaction between ET-1 and [Ca2+]e influences PTH secretion. ET-1 > or = 10(-10) M, inhibited PTH secretion in a dose-dependent manner and significantly inhibited PTH secretion at a low or normal [Ca2+]e. At an ET-1 concentration of > or = 10(-10) M, the 'calcium-PTH' relation showed significant changes in physiological responses. The effect of ET-1 on intracellular calcium concentrations ([Ca2+]i) of bPTCs was studied using the fura 2 fluorescence method. We found that increasing doses of ET-1 induced a progressive increase in [Ca2+]i of bPTCs. Our results suggest that ET-1 secretion is inversely regulated by [Ca2+]e. ET-1 can inhibit PTH secretion and alter the parathyroid secretion pattern to various calcium stimuli. ET-1 also elevates [Ca2+]i and this may be a part of the intracellular signaling mechanisms involved in the inhibition of PTH secretion from bPTCs.
Chang
J M
JM
Division of Nephrology, Kaohsiung Medical College, Taiwan.
Lai
Y H
YH
Tsai
J H
JH
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D004347:Drug Interactions; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*
D019332:Endothelin-1; D010281:Parathyroid Hormone; D002118:Calcium