A-4. 副甲状腺ホルモンの血清カルシウム上昇作用と骨組織中サイクリックAMP

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The demonstration of the effect of parathyroid hormone (PTH) to stimulate skeletal adenyl cyclase activity in vitro and to enhance cyclic AMP content in young rat calvaria in vivo prompted us to study the cyclic AMP metabolism in rat calvaria correlating to the known hypercalcemic effect of PTH.
Cyclic AMP was extracted from the calvaria dissected from soft tissue in ice cold water and frozen by immersing in dry ice-aceton as described by Chase et al. Competitive binding assay for cyclic AMP in this bone extract was considerably disturbed by an unexplainable interference, so the fraction of the assay responsive to cyclic nucleotide phosphodiesterase was taken as “true cyclic AMP”.
Cyclic AMP content in calvaria of 4 weeks old, thyroparathyroidectomized rat was increased maximally at the end of two minutes infusion of 10 U PTH and returned to control level within 30 minutes (0 time: 0.34, 2 minutes: 2.25, 10 minutes: 0.82, 30 minutes: 0.35 nmoles/g wet tissue). Whether such transient but marked elevation of cyclic AMP content in skeletal tissue was essential for calcium mobilization was examined by studying the response of plasma calcium and cyclic AMP in calvaria to various dose of PTH. Plasma calcium was already increased by infusing 0.5 U of PTH in the absence of detectable change in cyclic AMP metabolism in the skeletal tissue.
Intraperitoneal administration of 10 U of PTH, although raised plasma calcium to comparable extent to intravenous dose, failed to demonstrate any significant elevation of cyclic AMP in calvaria
Hypercalcemic effect of PTH in the absence of change in skeletal cyclic AMP level was also observed in experiment in which EGTA solution was infused into intact rat. Intact rat was recovered from EGTA induced hypocalcemia within one hour, probably due to effective calcium mobilization by endogenous PTH. Even in theophylline pretreated rat, cyclic AMP content in calvaria would not show any significant rise.
The demonstration of hypercalcemic effect of PTH in the absence of change in skeletal cyclic AMP in several experimental conditions might mean the increase in cyclic AMP level required for the hypercalcemic effect of PTH was too small or too transient to be detected by the assay method employed. Any way, it could be concluded that marked increment of cyclic AMP content observed in rat calvaria given relatively high dose of PTH intravenously was not physiological response and was not essential for hypercalcemic effect of PTH.