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Am J Physiol Endocrinol Metab 257: E505-E513, 1989;
0193-1849/89 $5.00
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AJP - Endocrinology and Metabolism, Vol 257, Issue 4 E505-E513, Copyright © 1989 by American Physiological Society

ARTICLES

Adenine nucleotides mobilize cellular Ca2+ and inhibit parathyroid hormone secretion

E. F. Nemeth and L. M. Kosz
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.

Measurements of the concentration of intracellular free calcium [( Ca2+]i) were used to screen for the presence of Ca2+-mobilizing receptors on dissociated and purified bovine parathyroid cells loaded with fura-2. Among a wide variety of agents known to mobilize cellular Ca2+ in other cells, only ATP and certain other nucleotides were capable of altering [Ca2+]i in parathyroid cells. The addition of ATP or adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) (10-200 microM) to parathyroid cells evoked a rapid and transient increase that was followed by a small, steady-state increase in [Ca2+]i. Cytosolic Ca2+ transients elicited by ATP or ATP gamma S persisted in the absence of extracellular Ca2+ and presence of a mitochondrial uncoupler but were blocked by pretreatment with ionomycin or fluoride. Cytosolic Ca2+ transients elicited by ATP were inhibited by increased concentrations of extracellular Ca2+, Mg2+, or Sr2+. Conversely, ATP depressed increases in [Ca2+]i elicited by these extracellular divalent cations. Parathyroid hormone (PTH) secretion was inhibited by ATP gamma S but not by those nucleotides that were without effect on [Ca2+]i. Loading cells with 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and fura-2 blocked cytosolic Ca2+ transients elicited by ATP gamma S but did not block the inhibitory effects of ATP gamma S on PTH secretion. The results show that the activation of a calcium-mobilizing receptor, in this case by ATP gamma S, is sufficient to inhibit PTH secretion. This favors the view that extracellular Ca2+ acts via a Ca2+-mobilizing receptor to regulate PTH secretion.


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E. F. Nemeth, M. E. Steffey, L. G. Hammerland, B. C. P. Hung, B. C. Van Wagenen, E. G. DelMar, and M. F. Balandrin
Calcimimetics with potent and selective activity on the parathyroid calcium receptor
PNAS, March 31, 1998; 95(7): 4040 - 4045.
[Abstract] [Full Text] [PDF]


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