Parathyroid hormone increases cytosolic calcium of thymocytes.
Parathyroid hormone (PTH) has been implicated in the genesis of the abnormalities of the immune system in uremia. This action was attributed to the ability of PTH to augment entry of calcium and hence sustain an elevation of the basal level of cytosolic calcium ([Ca2+]i) in the cells of the immune system. However, direct evidence for such an action of the hormone on these cells is lacking. We examined whether PTH affects [Ca2+]i of rat thymocytes and the potential mechanisms of such an effect. 1-84 PTH (0.5, 1.0, 2.0 x 10(-7) M) increased [Ca2+]i in a dose-dependent manner by 31 +/- 2.6, 73 +/- 3.8, and 128 +/- 10.8 nM, respectively. 1-34 PTH had no effect. The various doses of PTH antagonist ([Tyr-34] bPTH (7-34)NH2) blocked the PTH-induced rise in [Ca2+]i by 41-67%. Dibutyryl adenosine 3',5'-cyclic phosphatase (cAMP), forskolin and phorbol ester 12-0-tetradecanoyl-phorbol 13-acetate (TPA) also produced a significant rise in [Ca2+]i of thymocytes. Verapamil blocked the PTH action by 44% but had no effect on the dibutyryl-cAMP-, forskolin- or TPA-induced rise in [Ca2+]i. Absence of calcium in the media abolished the PTH-induced increase in [Ca2+]i and significantly reduced that of dibutyryl cAMP. Staurosporine completely prevented the TPA-induced rise in [Ca2+]i but had no effect on that produced by PTH. 1-84 PTH in the presence of calcium in the medium produced a significant rise in thymocyte cAMP but had no effect in the absence of calcium in the media.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Nephrology, University of Southern California School of Medicine, Los Angeles.
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O
Stojceva-Taneva
G Z
GZ
Fadda
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Smogorzewski
S G
SG
Massry
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D019379:Teriparatide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014511:Uremia / Q000276:immunology / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D005576:Colforsin; D003994:Bucladesine; C038040:parathyroid hormone (7-34)amide, Tyr(34)-; D014700:Verapamil; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium