Adenine nucleotides mobilize cellular Ca2+ and inhibit parathyroid hormone secretion.
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.
Nemeth
E F
EF
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Kosz
L M
LM
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D005459:Fluorides / Q000494:pharmacology; D016257:Fura-2; D007700:Kinetics; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology*; D013324:Strontium / Q000494:pharmacology
D000227:Adenine Nucleotides; D001572:Benzofurans; D005456:Fluorescent Dyes; D012265:Ribonucleotides; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D005459:Fluorides; D002118:Calcium; D016257:Fura-2; D004298:Dopamine; D013324:Strontium