PARATHYROID-HORMONE INCREASES CYTOSOLIC CALCIUM OF THYMOCYTES

Parathyroid hormone (PTH) has been implicated in the genesis of the ab normalities of the immune system in uremia. This action was attributed to the ability of PTH to augment entry of calcium and hence sustain a n elevation of the basal level of cytosolic calcium ([Ca2+]i) in the c ells of the immune system. However, direct evidence for such an action of the hormone on these cells is lacking. We examined whether PTH aff ects [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 do se-dependent manner by 31 +/- 2.6,73 +/- 3.8, and 128 +/- 10.8 nM, res pectively. 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 4 1-67%. Dibutyryl adenosine 3',5'-cyclic phosphatase (cAMP), forskolin and phorbol ester 12-0-tetradecanoyl-phorbol 13-acetate (TPA) also pro duced a significant rise in [Ca2+]i of thymocytes. Verapamil blocked t he PTH action by 44% but had no effect on the dibutyryl-cAMP-, forskol in- or TPA-induced rise in [Ca2+]i. Absence of calcium in the media ab olished the PTH-induced increase in [Ca2+]i and significantly reduced that of dibutyryl cAMP. Staurosprine completely prevented the TPA-indu ced rise in [Ca2+]i but had no effect on that produced by PTH. 1-84 PT H 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. The data indicate that (1) thymocytes are a target for PTH and that the intact hormones increased their [Ca2+]i, most likely, through a receptor-hormone interaction, (2) this action of the hormone appear s to be partially mediated by its stimulation of cAMP generation and p artially by activation of voltage-gated calcium channels, and (3) the rise in [Ca2+]i is, most likely due to both entry of calcium into the thymocytes and mobilization of calcium stores within the cells.